soutaro/published_papers/54106589 Mami Matsuda-Lennikov Jamie-Jean De La Torre Todd Snow Jacqueline Battaile Felix Kalle-Youngoue Alison Jacques Aya Ushio Akihide Shimizu Miho Shinzawa Christian T Mayer Parirokh Awasthi Raj Chari Izumi Ohigashi Shigeo Murata Yousuke Takahama Proteasome alteration between epithelial and hematopoietic cells facilitates positive selection of CD8 T cells. The thymoproteasome, a proteolytic complex uniquely expressed in cortical thymic epithelial cells (cTECs), governs the positive selection of CD8 T cells. It has been hypothesized that the thymoproteasome promotes CD8 T cell development by forging a sequential switch in proteasome species between cTECs and medullary antigen-presenting cells (APCs), which generates a stepwise difference in MHC-I-associated peptides between cTECs and medullary APCs, thereby sparing positively selected thymocytes from subsequent negative selection. In this study, we engineer mice ectopically expressing thymoproteasomes in various APCs including medullary TECs (mTECs), eliminating the proposed proteasome switch. Surprisingly, we find that the proteasome switch between cTECs and mTECs is dispensable for thymoproteasome-dependent CD8 T cell development. Instead, we find that ectopic thymoproteasomes in hematopoietic cells impair CD8 T cell development by hindering cortical positive selection. Our findings reveal that the proteasome difference between cTECs and hematopoietic cells in the thymic cortex facilitates thymoproteasome-dependent positive selection. Nature communications null null 20260427 10.1038/s41467-026-72411-x 42045195 soutaro/published_papers/51474378 Naoko Matsui 松井 尚子 Izumi Ohigashi 大東 いずみ Alexander Marx Thymus research in relation to myasthenia gravis: a new perspective on cell subpopulations and future directions Thymus research in relation to myasthenia gravis : a new perspective on cell subpopulations and future directions The thymus generates T cells from immature thymocytes and prevents autoimmune diseases through negative selection and the generation of FOXP3⁺ regulatory T cells (Tregs). The thymic architecture is typically divided into two distinct microenvironments, the cortex and the medulla. These microenvironments are characterized by the presence of cortical thymic epithelial cells (cTECs) and medullary thymic epithelial cells (mTECs), respectively. Recent single-cell and spatial transcriptomic analyses have revealed the expanding diversity of TEC subpopulations in mice and humans. Myasthenia gravis (MG) is an autoimmune disorder characterized by fatigue resulting from muscle weakness, which is caused by antibodies toward structures within the neuromuscular junction. The most common target of pathogenic autoantibodies in MG is the acetylcholine receptor (AChR). MG patients are prone to thymic abnormalities, including thymic follicular hyperplasia and thymoma. Previous studies have suggested that mTECs expressing major histocompatibility complex (MHC)/AChR–peptide complexes are involved in the intrathymic pathogenesis of this MG type. However, the exact mechanisms are unknown. This review provides an update on the diversity of TEC subpopulations and other cellular alterations in the MG thymus. Additionally, we present hypotheses on the pathogenetic pathways leading to MG and suggest potential future directions in thymus research. Frontiers Media SA Frontiers in Immunology 1664-3224 16 1649171 null null 20251014 10.3389/fimmu.2025.1649171 soutaro/published_papers/48391068 Graham Anderson Emilie J Cosway Kieran D James Izumi Ohigashi Yousuke Takahama Generation and repair of thymic epithelial cells. In the vertebrate immune system, thymus stromal microenvironments support the generation of αβT cells from immature thymocytes. Thymic epithelial cells are of particular importance, and the generation of cortical and medullary epithelial lineages from progenitor stages controls the initiation and maintenance of thymus function. Here, we discuss the developmental pathways that regulate thymic epithelial cell diversity during both the embryonic and postnatal periods. We also examine how thymus microenvironments respond to injury, with particular focus on mechanisms that ensure regeneration of thymic epithelial cells for the restoration of thymus function. The Journal of experimental medicine 221 10 null null 20241007 10.1084/jem.20230894 38980292 soutaro/published_papers/46120699 Izumi Ohigashi Mami Matsuda-Lennikov Yousuke Takahama Large-Scale Isolation of Mouse Thymic Epithelial Cells. The thymus is compartmentalized into the cortex and the medulla. Cortical and medullary thymic epithelial cells (TECs) characterize T cell-producing and T cell-selecting functions of cortical and medullary microenvironments in the thymus. Enzymatic digestion of the thymus and flow cytometric isolation of TECs and their subpopulations are useful for molecular and cellular characterization of TECs. However, the cellularity of cTECs and mTECs isolated from mouse thymus is limited. In this chapter, we describe the method for isolation of a large number of TECs using enlarged mouse thymus, which enables biochemical and proteomic analysis of TEC subpopulations. Methods in molecular biology (Clifton, N.J.) 2580 189 197 20230000 10.1007/978-1-0716-2740-2_11 36374458 soutaro/published_papers/40949895 Yang Zhang Laura Garcia-Ibanez Carolin Ulbricht Laurence S. C. Lok Jeremy A. Pike Jennifer Mueller-Winkler Thomas W. Dennison John R. Ferdinand Cameron J. M. Burnett Juan C. Yam-Puc Lingling Zhang Raul Maqueda Alfaro Yousuke Takahama Izumi Ohigashi Geoffrey Brown Tomohiro Kurosaki Victor L. J. Tybulewicz Antal Rot Anja E. Hauser Menna R. Clatworthy Kai-Michael Toellner Recycling of memory B cells between germinal center and lymph node subcapsular sinus supports affinity maturation to antigenic drift Abstract Infection or vaccination leads to the development of germinal centers (GC) where B cells evolve high affinity antigen receptors, eventually producing antibody-forming plasma cells or memory B cells. Here we follow the migratory pathways of B cells emerging from germinal centers (B_EM) and find that many B_EM cells migrate into the lymph node subcapsular sinus (SCS) guided by sphingosine-1-phosphate (S1P). From the SCS, B_EM cells may exit the lymph node to enter distant tissues, while some B_EM cells interact with and take up antigen from SCS macrophages, followed by CCL21-guided return towards the GC. Disruption of local CCL21 gradients inhibits the recycling of B_EM cells and results in less efficient adaption to antigenic variation. Our findings thus suggest that the recycling of antigen variant-specific B_EM cells and transport of antigen back to GC may support affinity maturation to antigenic drift. Springer Science and Business Media LLC Nature Communications 2041-1723 13 1 null null 20221200 10.1038/s41467-022-29978-y soutaro/published_papers/40746011 Mami Matsuda-Lennikov Izumi Ohigashi Yousuke Takahama Tissue-specific proteasomes in generation of MHC class I peptides and CD8+ T cells. Thymoproteasomes and immunoproteasomes are two types of tissue-specific proteasomes, which contribute to the production of major histocompatibility complex (MHC) class I (MHC-I)-associated peptides that are important for the development and function of CD8+ cytotoxic T cells. Thymoproteasomes are specifically expressed by cortical thymic epithelial cells and are important for MHC-I-dependent positive selection of developing thymocytes, whereas immunoproteasomes are abundant in many other cells, including hematopoietic cells and medullary thymic epithelial cells. Here we summarize the role of these two tissue-specific proteasomes, focusing on their functions in the development of CD8+ T cells in the thymus. Current opinion in immunology 77 102217 102217 20220800 10.1016/j.coi.2022.102217 35689940 soutaro/published_papers/34002450 Yohei Yamamoto Naoko Matsui Akiyuki Uzawa Yukiko Ozawa Tetsuya Kanai Fumiko Oda Hiroyuki Kondo Izumi Ohigashi Hiromitsu Takizawa Kazuya Kondo Mikio Sugano Takashi Kitaichi Hiroki Hata Ryuji Kaji Satoshi Kuwabara Takashi Yamamura Yuishin Izumi Intrathymic Plasmablasts Are Affected in Patients With Myasthenia Gravis With Active Disease. BACKGROUND AND OBJECTIVES: To investigate intrathymic B lymphopoiesis in patients with myasthenia gravis (MG) and explore thymus pathology associated with clinical impact. METHODS: Thymic lymphocytes from 15 young patients without MG, 22 adult patients without MG, 14 patients with MG without thymoma, and 11 patients with MG with thymoma were subjected to flow cytometry analysis of T follicular helper (Tfh), naive B, memory B, plasmablasts, CD19+B220high thymic B cells, B-cell activating factor receptor, and C-X-C chemokine receptor 5 (CXCR5). Peripheral blood mononuclear cells of 16 healthy subjects and 21 untreated patients with MG were also analyzed. Immunologic values were compared, and correlations between relevant values and clinical parameters were evaluated. RESULTS: The frequencies of circulating and intrathymic plasmablasts were significantly higher in patients with MG than controls. On the other hand, the frequency of CD19+B220high thymic B cells was not increased in MG thymus. We observed a significant increase in CXCR5 expression on plasmablasts in MG thymus and an increased frequency of intrathymic plasmablasts that was correlated with preoperative disease activity. The frequency of intrathymic Tfh cells was significantly lower in patients who received immunosuppressive (IS) therapy than those without IS therapy. However, there was no significant difference in the frequency of intrathymic plasmablasts irrespective of IS therapy. DISCUSSION: Our findings confirmed a correlation between increased frequency of intrathymic plasmablasts and disease activity before thymectomy. We postulate that activated intrathymic plasmablasts endow pathogenic capacity in MG. Neurology(R) neuroimmunology & neuroinflammation 8 6 null null 20211100 10.1212/NXI.0000000000001087 34561276 soutaro/published_papers/34002449 Izumi Ohigashi Mami Matsuda-Lennikov Yousuke Takahama Peptides for T cell selection in the thymus. Major histocompatibility complex (MHC)-associated peptides generated and displayed by antigen-presenting cells in the thymus are essential for the generation of functional and self-tolerant T cells that protect our body from various pathogens. The peptides displayed by cortical thymic epithelial cells (cTECs) are generated by unique enzymatic machineries including the thymoproteasomes, and are involved in the positive selection of self-protective T cells. On the other hand, the peptides displayed by medullary thymic epithelial cells (mTECs) and thymic dendritic cells (DCs) are involved in further selection to establish self-tolerance in T cells. Although the biochemical nature of the peptide repertoire displayed in the thymus remains unclear, many studies have suggested a thymus-specific mechanism for the generation of MHC-associated peptides in the thymus. In this review, we summarize basic knowledge and recent advances in MHC-associated thymic peptides, focusing on the generation and function of thymoproteasome-dependent peptides specifically displayed by cTECs. Peptides 146 170671 170671 20211005 10.1016/j.peptides.2021.170671 34624431 soutaro/published_papers/34002451 Izumi Ohigashi Yousuke Takahama Specific impact of β5t on proteasome subunit composition in cortical thymic epithelial cells. β5t is a cortical thymic epithelial cell (cTEC)-specific component of the thymoproteasome, which is essential for the optimal production of functionally competent CD8+ T cells. Our recent analysis showed a specific impact of β5t on proteasome subunit composition in cTECs, supporting the possibility that the thymoproteasome optimizes CD8+ T cell development through the production of MHC-I-associated unique self-peptides in cTECs. However, a recent article reports that β5t regulates the expression of hundreds of cTEC genes and affects both CD4+ and CD8+ thymocytes by causing oxidative stress in thymocytes. The authors further analyze our published data and describe that they confirm their conclusions. Here, we examine the issues that they raise and conclude that, rather than regulating hundreds of genes in cTECs, β5t has a highly specific impact in cTECs on proteasome subunit composition. This Matters Arising Response article addresses the Apavaloaei et al. (2021) Matters Arising paper, published concurrently in Cell Reports. Cell reports 36 10 109657 109657 20210907 10.1016/j.celrep.2021.109657 34496235 soutaro/published_papers/31458315 Kieran D. James Daniel F. Legler Vladimir Purvanov Izumi Ohigashi Yousuke Takahama Sonia M. Parnell Andrea J. White William E. Jenkinson Graham Anderson Medullary stromal cells synergize their production and capture of CCL21 for T-cell emigration from neonatal mouse thymus <title>Abstract</title> The release of newly selected αβT cells from the thymus is key in establishing a functional adaptive immune system. Emigration of the first cohorts of αβT cells produced during the neonatal period is of particular importance, because it initiates formation of the peripheral αβT-cell pool and provides immune protection early in life. Despite this, the cellular and molecular mechanisms of thymus emigration are poorly understood. We examined the involvement of diverse stromal subsets and individual chemokine ligands in this process. First, we demonstrated functional dichotomy in the requirement for CCR7 ligands and identified CCL21, but not CCL19, as an important regulator of neonatal thymus emigration. To explain this ligand-specific requirement, we examined sites of CCL21 production and action and found Ccl21 gene expression and CCL21 protein distribution occurred within anatomically distinct thymic areas. Although Ccl21 transcription was limited to subsets of medullary epithelium, CCL21 protein was captured by mesenchymal stroma consisting of integrin α7+ pericytes and CD34+ adventitial cells at sites of thymic exit. This chemokine compartmentalization involved the heparan sulfate–dependent presentation of CCL21 via its C-terminal extension, explaining the absence of a requirement for CCL19, which lacks this domain and failed to be captured by thymic stroma. Collectively, we identified an important role for CCL21 in neonatal thymus emigration, revealing the importance of this chemokine in initial formation of the peripheral immune system. Moreover, we identified an intrathymic mechanism involving cell-specific production and presentation of CCL21, which demonstrated a functional synergy between thymic epithelial and mesenchymal cells for αβT-cell emigration. American Society of Hematology Blood Advances 2473-9537 5 1 99 112 20210112 10.1182/bloodadvances.2020003192 soutaro/published_papers/34002455 Melina Frantzeskakis Yousuke Takahama Izumi Ohigashi The Role of Proteasomes in the Thymus. The thymus provides a microenvironment that supports the generation and selection of T cells. Cortical thymic epithelial cells (cTECs) and medullary thymic epithelial cells (mTECs) are essential components of the thymic microenvironment and present MHC-associated self-antigens to developing thymocytes for the generation of immunocompetent and self-tolerant T cells. Proteasomes are multicomponent protease complexes that degrade ubiquitinated proteins and produce peptides that are destined to be associated with MHC class I molecules. cTECs specifically express thymoproteasomes that are essential for optimal positive selection of CD8+ T cells, whereas mTECs, which contribute to the establishment of self-tolerance in T cells, express immunoproteasomes. Immunoproteasomes are also detectable in dendritic cells and developing thymocytes, additionally contributing to T cell development in the thymus. In this review, we summarize the functions of proteasomes expressed in the thymus, focusing on recent findings pertaining to the functions of the thymoproteasomes and the immunoproteasomes. Frontiers in immunology 12 646209 646209 20210000 10.3389/fimmu.2021.646209 33815406 soutaro/published_papers/34002454 Izumi Ohigashi Yousuke Takahama Thymoproteasome optimizes positive selection of CD8+ T cells without contribution of negative selection. Functionally competent and self-tolerant T cell repertoire is shaped through positive and negative selection in the cortical and medullary microenvironments of the thymus. The thymoproteasome specifically expressed in the cortical thymic epithelium is essential for the optimal generation of CD8+ T cells. Although how the thymoproteasome governs the generation of CD8+ T cells is not fully understood, accumulating evidence suggests that the thymoproteasome optimizes CD8+ T cell production through the processing of self-peptides associated with MHC class I molecules expressed by cortical thymic epithelial cells. In this review, we describe recent advances in the mechanism of thymoproteasome-dependent generation of CD8+ T cells, focusing on the process of cortical positive selection independent of apoptosis-mediated negative selection. Advances in immunology 149 1 23 20210000 10.1016/bs.ai.2021.03.001 33993918 soutaro/published_papers/34002453 Marita Bosticardo Izumi Ohigashi Jennifer E Cowan Nuno L Alves Editorial: Thymic Epithelial Cells: New Insights Into the Essential Driving Force of T-Cell Differentiation. Frontiers in immunology 12 744623 744623 20210000 10.3389/fimmu.2021.744623 34484248 soutaro/published_papers/31458305 Mercedes Lachén-Montes Naroa Mendizuri Karina Ausín Alberto Pérez-Mediavilla Mikel Azkargorta Ibon Iloro Felix Elortza Hiroyuki Kondo Izumi Ohigashi Isidre Ferrer Rafael de la Torre Patricia Robledo Joaquín Fernández-Irigoyen Enrique Santamaría Smelling the Dark Proteome: Functional Characterization of PITH Domain-Containing Protein 1 (C1orf128) in Olfactory Metabolism The Human Proteome Project (HPP) consortium aims to functionally characterize the dark proteome. On the basis of the relevance of olfaction in early neurodegeneration, we have analyzed the dark proteome using data mining in public resources and omics data sets derived from the human olfactory system. Multiple dark proteins localize at synaptic terminals and may be involved in amyloidopathies such as Alzheimer's disease (AD). We have characterized the dark PITH domain-containing protein 1 (PITHD1) in olfactory metabolism using bioinformatics, proteomics, in vitro and in vivo studies, and neuropathology. PITHD1-/- mice exhibit olfactory bulb (OB) proteome changes related to synaptic transmission, cognition, and memory. OB PITHD1 expression increases with age in wild-type (WT) mice and decreases in Tg2576 AD mice at late stages. The analysis across 6 neurological disorders reveals that olfactory tract (OT) PITHD1 is specifically upregulated in human AD. Stimulation of olfactory neuroepithelial (ON) cells with PITHD1 alters the ON phosphoproteome, modifies the proliferation rate, and induces a pro-inflammatory phenotype. This workflow applied by the Spanish C-HPP and Human Brain Proteome Project (HBPP) teams across the ON-OB-OT axis can be adapted as a guidance to decipher functional features of dark proteins. Data are available via ProteomeXchange with identifiers PXD018784 and PXD021634. American Chemical Society (ACS) Journal of Proteome Research 1535-3907 19 12 4826 4843 20201204 10.1021/acs.jproteome.0c00452 33185454 soutaro/published_papers/30302116 Pedro Ferreirinha Camila Ribeiro Junko Morimoto Jonathan J. M. Landry Minoru Matsumoto Catarina Meireles Andrea J. White Izumi Ohigashi Leonor Araújo Vladimir Benes Yousuke Takahama Graham Anderson Mitsuru Matsumoto Nuno L. Alves A novel method to identify Post‐Aire stages of medullary thymic epithelial cell differentiation Autoimmune regulator+ (Aire) medullary thymic epithelial cells (mTECs) play a critical role in tolerance induction. Several studies demonstrated that Aire+ mTECs differentiate further into Post-Aire cells. Yet, the identification of terminal stages of mTEC maturation depends on unique fate-mapping mouse models. Herein, we resolve this limitation by segmenting the mTEChi (MHCIIhi CD80hi ) compartment into mTECA/hi (CD24- Sca1- ), mTECB/hi (CD24+ Sca1- ), and mTECC/hi (CD24+ Sca1+ ). While mTECA/hi included mostly Aire-expressing cells, mTECB/hi contained Aire+ and Aire- cells and mTECC/hi were mainly composed of cells lacking Aire. The differential expression pattern of Aire led us to investigate the precursor-product relationship between these subsets. Strikingly, transcriptomic analysis of mTECA/hi , mTECB/hi , and mTECC/hi sequentially mirrored the specific genetic program of Early-, Late- and Post-Aire mTECs. Corroborating their Post-Aire nature, mTECC/hi downregulated the expression of tissue-restricted antigens, acquired traits of differentiated keratinocytes, and were absent in Aire-deficient mice. Collectively, our findings reveal a new and simple blueprint to survey late stages of mTEC differentiation. Wiley European Journal of Immunology 1521-4141 null null 20200915 10.1002/eji.202048764 32845012 soutaro/published_papers/27856172 Beth Lucas Andrea J White Emilie J Cosway Sonia M Parnell Kieran D James Nick D Jones Izumi Ohigashi Yousuke Takahama William E Jenkinson Graham Anderson Diversity in medullary thymic epithelial cells controls the activity and availability of iNKT cells. The thymus supports multiple αβ T cell lineages that are functionally distinct, but mechanisms that control this multifaceted development are poorly understood. Here we examine medullary thymic epithelial cell (mTEC) heterogeneity and its influence on CD1d-restricted iNKT cells. We find three distinct mTEClow subsets distinguished by surface, intracellular and secreted molecules, and identify LTβR as a cell-autonomous controller of their development. Importantly, this mTEC heterogeneity enables the thymus to differentially control iNKT sublineages possessing distinct effector properties. mTEC expression of LTβR is essential for the development thymic tuft cells which regulate NKT2 via IL-25, while LTβR controls CD104+CCL21+ mTEClow that are capable of IL-15-transpresentation for regulating NKT1 and NKT17. Finally, mTECs regulate both iNKT-mediated activation of thymic dendritic cells, and iNKT availability in extrathymic sites. In conclusion, mTEC specialization controls intrathymic iNKT cell development and function, and determines iNKT pool size in peripheral tissues. Nature communications 11 1 2198 2198 20200504 10.1038/s41467-020-16041-x 32366944 soutaro/published_papers/24541717 Hiroyuki Kondo Takafumi Matsumura Mari Kaneko Kenichi Inoue Hidetaka Kosako Masahito Ikawa Yousuke Takahama Izumi Ohigashi PITHD1 is a proteasome-interacting protein essential for male fertilization. The proteasome is a protein-degrading molecular complex that is necessary for protein homeostasis and various biological functions, including cell cycle regulation, signal transduction, and immune response. Proteasome activity is finely regulated by a variety of proteasome-interacting molecules. PITHD1 is a recently described molecule that has a domain putatively capable of interacting with the proteasome. However, it is unknown whether PITHD1 can actually bind to proteasomes and what it does in vivo Here we report that PITHD1 is detected specifically in the spermatids in the testis and the cortical thymic epithelium in the thymus. Interestingly, PITHD1 associates with immunoproteasomes in the testis, but not with thymoproteasomes in the thymus. Mice deficient in PITHD1 exhibit severe male infertility accompanied with morphological abnormalities and impaired motility of spermatozoa. Furthermore, PITHD1 deficiency reduces proteasome activity in the testis and alters the amount of proteins that are important for fertilization capability by the sperm. However, the PITHD1-deficient mice demonstrate no detectable defects in the thymus, including T cell development. Collectively, our results identify PITHD1 as a proteasome-interacting protein that plays a nonredundant role in the male reproductive system. The Journal of biological chemistry 295 6 1658 1672 20200207 10.1074/jbc.RA119.011144 31915251 soutaro/published_papers/27856171 Jennifer E Cowan Yousuke Takahama Avinash Bhandoola Izumi Ohigashi Postnatal Involution and Counter-Involution of the Thymus. Thymus involution occurs in all vertebrates. It is thought to impact on immune responses in the aged, and in other clinical circumstances such as bone marrow transplantation. Determinants of thymus growth and size are beginning to be identified. Ectopic expression of factors like cyclin D1 and Myc in thymic epithelial cells (TEC)s results in considerable increase in thymus size. These models provide useful experimental tools that allow thymus function to be understood. In future, understanding TEC-specific controllers of growth will provide new approaches to thymus regeneration. Frontiers in immunology 11 897 897 20200000 10.3389/fimmu.2020.00897 32477366 soutaro/published_papers/24541718 Jennifer E Cowan Justin Malin Yongge Zhao Mina O Seedhom Christelle Harly Izumi Ohigashi Michael Kelly Yousuke Takahama Jonathan W Yewdell Maggie Cam Avinash Bhandoola Myc controls a distinct transcriptional program in fetal thymic epithelial cells that determines thymus growth. Interactions between thymic epithelial cells (TEC) and developing thymocytes are essential for T cell development, but molecular insights on TEC and thymus homeostasis are still lacking. Here we identify distinct transcriptional programs of TEC that account for their age-specific properties, including proliferation rates, engraftability and function. Further analyses identify Myc as a regulator of fetal thymus development to support the rapid increase of thymus size during fetal life. Enforced Myc expression in TEC induces the prolonged maintenance of a fetal-specific transcriptional program, which in turn extends the growth phase of the thymus and enhances thymic output; meanwhile, inducible expression of Myc in adult TEC similarly promotes thymic growth. Mechanistically, this Myc function is associated with enhanced ribosomal biogenesis in TEC. Our study thus identifies age-specific transcriptional programs in TEC, and establishes that Myc controls thymus size. Nature communications 10 1 5498 5498 20191202 10.1038/s41467-019-13465-y 31792212 soutaro/published_papers/24541719 Izumi Ohigashi Yu Tanaka Kenta Kondo Sayumi Fujimori Hiroyuki Kondo Amy C Palin Victoria Hoffmann Mina Kozai Yosuke Matsushita Shinsuke Uda Ryo Motosugi Jun Hamazaki Hiroyuki Kubota Shigeo Murata Keiji Tanaka Toyomasa Katagiri Hidetaka Kosako Yousuke Takahama Trans-omics Impact of Thymoproteasome in Cortical Thymic Epithelial Cells. The thymic function to produce self-protective and self-tolerant T cells is chiefly mediated by cortical thymic epithelial cells (cTECs) and medullary TECs (mTECs). Recent studies including single-cell transcriptomic analyses have highlighted a rich diversity in functional mTEC subpopulations. Because of their limited cellularity, however, the biochemical characterization of TECs, including the proteomic profiling of cTECs and mTECs, has remained unestablished. Utilizing genetically modified mice that carry enlarged but functional thymuses, here we show a combination of proteomic and transcriptomic profiles for cTECs and mTECs, which identified signature molecules that characterize a developmental and functional contrast between cTECs and mTECs. Our results reveal a highly specific impact of the thymoproteasome on proteasome subunit composition in cTECs and provide an integrated trans-omics platform for further exploration of thymus biology. Cell reports 29 9 2901 2916 20191126 10.1016/j.celrep.2019.10.079 31775054 soutaro/published_papers/24541720 Umme Shahina Khanom Izumi Ohigashi Sayumi Fujimori Kenta Kondo Kensuke Takada Yousuke Takahama TCR Affinity for In Vivo Peptide-Induced Thymic Positive Selection Fine-Tunes TCR Responsiveness of Peripheral CD8+ T Cells. The affinity for TCR interactions with self-peptide/MHC complexes (pMHC) in the thymus critically affects immature thymocytes that newly express TCRs. Previous fetal thymus organ culture experiments have indicated that difference in the affinity for thymic TCR/pMHC interactions not only determines thymocyte fate between positive and negative selection, but also affects Ag responsiveness of positively selected thymocytes. In the current study, we examined whether TCR/pMHC affinity during positive selection in the thymus would further affect Ag responsiveness of mature T cells in the periphery. To do so, OVA peptide variants were in vivo administered to TAP1-deficient OT-I/TCR-transgenic mice in which T cell development was otherwise arrested at CD4+CD8+ thymocytes because of the lack of self-pMHC presentation in thymic APCs. We found that a group of peptide variants induced the transient generation of OT-I CD8+ T cells in the thymus and the periphery. We also noticed that the affinity threshold for positive and negative selection detected in adult mice in vivo was higher than that measured in fetal thymus organ culture experiments in vitro. Interestingly, we further found that the affinity for positively selecting peptides proportionally affected TCR responsiveness of peripheral naive CD8+ T cells. These results indicate that in vivo administration of a peptide can promote T cell selection in the thymus and the affinity for TCR/pMHC interaction during positive selection fine-tunes Ag responsiveness of peripheral T cells. Journal of immunology (Baltimore, Md. : 1950) 203 4 881 887 20190815 10.4049/jimmunol.1900097 31235550 soutaro/published_papers/24541702 Kenta Kondo Izumi Ohigashi Yousuke Takahama Thymus machinery for T-cell selection. Oxford University Press (OUP) International Immunology 1460-2377 31 3 119 125 20190305 10.1093/intimm/dxy081 soutaro/published_papers/14796717 Takahama Y Ohigashi I Murata S Tanaka K Thymoproteasome and peptidic self. Springer Science and Business Media LLC Immunogenetics 1432-1211 71 3 217 221 20181000 10.1007/s00251-018-1081-3 30324237 soutaro/published_papers/14796677 EJ Cosway Izumi Ohigashi K Schauble SM Parnell WE Jenkinson S Luther Yousuke Takahama G Anderson Formation of the intrathymic dendritic cell pool requires CCL21-mediated recruitment of CCR7+ progenitors to the thymus The American Association of Immunologists The Journal of Immunology 1550-6606 201 2 516 523 20180700 10.4049/jimmunol.1800348 29784760 soutaro/published_papers/14796678 Mie Sakata Izumi Ohigashi Yousuke Takahama Cellularity of thymic epithelial cells in the postnatal mouse American Association of Immunologists Journal of Immunology 1550-6606 200 4 1382 1388 20180215 10.4049/jimmunol.1701235 29298829 2-s2.0-85044773413 soutaro/published_papers/14796718 Takeuchi A Ozawa M Kanda Y Kozai M Ohigashi I Kurosawa Y Rahman MA Kawamura T Shichida Y Umemoto E Miyasaka M Ludewig B Takahama Y Nagasawa T Katakai T A Distinct Subset of Fibroblastic Stromal Cells Constitutes the Cortex-Medulla Boundary Subcompartment of the Lymph Node. The spatiotemporal regulation of immune responses in the lymph node (LN) depends on its sophisticated tissue architecture, consisting of several subcompartments supported by distinct fibroblastic stromal cells (FSCs). However, the intricate details of stromal structures and associated FSC subsets are not fully understood. Using several gene reporter mice, we sought to discover unrecognized stromal structures and FSCs in the LN. The four previously identified FSC subsets in the cortex are clearly distinguished by the expression pattern of reporters including PDGFRβ, CCL21-ser, and CXCL12. Herein, we identified a unique FSC subset expressing both CCL21-ser and CXCL12 in the deep cortex periphery (DCP) that is characterized by preferential B cell localization. This subset was clearly different from CXCL12highLepRhigh FSCs in the medullary cord, which harbors plasma cells. B cell localization in the DCP was controlled chiefly by CCL21-ser and, to a lesser extent, CXCL12. Moreover, the optimal development of the DCP as well as medulla requires B cells. Together, our findings suggest the presence of a unique microenvironment in the cortex-medulla boundary and offer an advanced view of the multi-layered stromal framework constructed by distinct FSC subsets in the LN. Frontiers in immunology 9 2196 2196 20180000 10.3389/fimmu.2018.02196 30333825 soutaro/published_papers/25201800 Mina Kozai Yuki Kubo Tomoya Katakai Hiroyuki Kondo Hiroshi Kiyonari Karin Schaeuble Sanjiv A. Luther Naozumi Ishimaru Izumi Ohigashi Yousuke Takahama Essential role of CCL21 in establishment of central self-tolerance in T cells JOURNAL OF EXPERIMENTAL MEDICINE 1540-9538 214 7 1925 1935 20170700 10.1084/jem.20161864 28611158 soutaro/published_papers/14796680 Izumi Ohigashi Yuki Ohte Kazuya Setoh Hiroshi Nakase Akiko Maekawa Hiroshi Kiyonari Yoko Hamazaki Miho Sekai Tetsuo Sudo Yasuharu Tabara Hiromi Sawai Yosuke Omae Rika Yuliwulandari Yasuhito Tanaka Masashi Mizokami Hiroshi Inoue Masanori Kasahara Nagahiro Minato Katsushi Tokunaga Keiji Tanaka Fumihiko Matsuda Shigeo Murata Yousuke Takahama A human PSMB11 variant affects thymoproteasome processing and CD8+ T cell production JCI Insight 2379-3708 2 10 null null 20170518 10.1172/jci.insight.93664 28515360 soutaro/published_papers/14796681 Muhammad Myn Uddin Izumi Ohigashi Ryo Motosugi Tomomi Nakayama Mie Sakata Jun Hamazaki Yasumasa Nishito Immanuel Rode Keiji Tanaka Tatsuya Takemoto Shigeo Murata Yousuke Takahama Foxn1-beta 5t transcriptional axis controls CD8(+) T-cell production in the thymus NATURE COMMUNICATIONS 2041-1723 8 14419 14419 20170200 10.1038/ncomms14419 28176764 soutaro/published_papers/14796682 Izumi Ohigashi Mina Kozai Yousuke Takahama Development and developmental potential of cortical thymic epithelial cells The thymic cortex provides a microenvironment for the development and positive selection of immature T cells. Cortical thymic epithelial cells (cTECs), which structurally and functionally support the thymic cortical microenvironment, originate from endodermal epithelial progenitors that arise in the third pharyngeal pouch. Recent studies have revealed that thymic epithelial progenitors pass through a stage where the cells express cTEC-associated molecules prior to lineage separation into cTECs and medullary TECs (mTECs). Here, we review the molecular signatures of cTECs and highlight the development and developmental potential of cTECs. Immunological Reviews 1600-065X 271 1 10 22 20160500 10.1111/imr.12404 27088904 soutaro/published_papers/28158753 Carlos E. Mayer Saulius Zuklys Saule Zhanybekova Izumi Ohigashi Hong-Ying Teh Stephen N. Sansom Noriko Shikama-Dorn Katrin Hafen Iain C. Macaulay Mary E. Deadman Chris P. Ponting Yousuke Takahama Georg A. Hollaender Dynamic spatio-temporal contribution of single beta 5t+cortical epithelial precursors to the thymus medulla EUROPEAN JOURNAL OF IMMUNOLOGY 1521-4141 46 4 846 856 20160400 10.1002/eji.201545995 soutaro/published_papers/14796685 Izumi Ohigashi Yousuke Takahama Flow Cytometry Analysis of Thymic Epithelial Cells and Their Subpopulations The parenchyma of the thymus is compartmentalized into the cortex and the medulla, which are constructed by cortical thymic epithelial cells (cortical TECs, cTECs) and medullary thymic epithelial cells (mTECs), respectively. cTECs and mTECs essentially and differentially regulate the development and repertoire selection of T cells. Consequently, the biology of T cell development and selection includes the study of TECs in addition to the study of developing T cells and other hematopoietic cells including dendritic cells. In this chapter, we describe the methods for flow cytometric analysis and sorting of TECs and their subpopulations, including cTECs and mTECs. Springer New York Methods in Molecular Biology 1940-6029 1323 65 73 20160000 10.1007/978-1-4939-2809-5_5 26294398 soutaro/published_papers/14796684 Izumi Ohigashi Yousuke Takahama Thymocyte-mTEC cross talk for self-tolerance in T cells Encyclopedia of Immunology 1 263 267 20160000 soutaro/published_papers/14796686 Izumi Ohigashi Saulius Zuklys Mie Sakata Carlos E. Mayer Yoko Hamazaki Nagahiro Minato Georg A. Hollander Yousuke Takahama Adult Thymic Medullary Epithelium Is Maintained and Regenerated by Lineage-Restricted Cells Rather Than Bipotent Progenitors CELL REPORTS 2211-1247 13 7 1432 1443 20151100 10.1016/j.celrep.2015.10.012 26549457 soutaro/published_papers/14796689 Izumi Ohigashi Yousuke Takahama CCRL1 marks heterogeneity in cortical and medullary thymic epithelial cells Wiley-VCH Verlag European Journal of Immunology 1521-4141 44 10 2872 2875 20141001 10.1002/eji.201445091 25216053 2-s2.0-84925236502 soutaro/published_papers/28040181 Naoko Matsui Izumi Ohigashi Keijirou Tanaka Mie Sakata Takahiro Furukawa Yasushi Nakagawa Kazuya Kondo Tetsuya Kitagawa Sumimasa Yamashita Yoshiko Nomura Yousuke Takahama Ryuji Kaji Increased number of Hassall's corpuscles in myasthenia gravis patients with thymic hyperplasia JOURNAL OF NEUROIMMUNOLOGY 1872-8421 269 1-2 56 61 20140400 10.1016/j.jneuroim.2014.01.011 soutaro/published_papers/25858466 Joy A. Williams Jingjing Zhang Hyein Jeon Takeshi Nitta Izumi Ohigashi David Klug Michael J. Kruhlak Baishakhi Choudhury Susan O. Sharrow Larry Granger Anthony Adams Michael A. Eckhaus S. Rhiannon Jenkinson Ellen R. Richie Ronald E. Gress Yousuke Takahama Richard J. Hodes Thymic Medullary Epithelium and Thymocyte Self-Tolerance Require Cooperation between CD28-CD80/86 and CD40-CD40L Costimulatory Pathways JOURNAL OF IMMUNOLOGY 1550-6606 192 2 630 640 20140100 10.4049/jimmunol.1302550 24337745 soutaro/published_papers/14796688 Kensuke Takada Izumi Ohigashi Michiyuki Kasai Hiroshi Nakase Yousuke Takahama Development and Function of Cortical Thymic Epithelial Cells THYMIC DEVELOPMENT AND SELECTION OF T LYMPHOCYTES 0070-217X 373 1 17 20140000 10.1007/82_2013_322 23612989 soutaro/published_papers/14796687 Nuno L. Alves Yousuke Takahama Izumi Ohigashi Ana R. Ribeiro Song Baik Graham Anderson William E. Jenkinson Serial progression of cortical and medullary thymic epithelial microenvironments Wiley-VCH Verlag European Journal of Immunology 1521-4141 44 1 16 22 20140000 10.1002/eji.201344110 24214487 2-s2.0-84892472653 soutaro/published_papers/25861833 S. Rhiannon Jenkinson Joy A. Williams Hyein Jeon Jingjing Zhang Takeshi Nitta Izumi Ohigashi Michael Kruhlak Saulius Zuklys Susan Sharrow Anthony Adams Larry Granger Yongwon Choi Ulrich Siebenlist Gail A. Bishop Georg A. Hollander Yousuke Takahama Richard J. Hodes TRAF3 enforces the requirement for T cell cross-talk in thymic medullary epithelial development PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 0027-8424 110 52 21107 21112 20131200 10.1073/pnas.1314859111 24324158 soutaro/published_papers/25858463 Izumi Ohigashi Ohigashi I Saulius Zuklys Zuklys S Mie Sakata Sakata M Carlos E. Mayer Mayer CE Saule Zhanybekova Zhanybekova S Shigeo Murata Murata S Keiji Tanaka Tanaka K Georg A. Hollaender Holländer GA Yousuke Takahama Takahama Y Aire-expressing thymic medullary epithelial cells originate from beta 5t-expressing progenitor cells Aire-expressing thymic medullary epithelial cells originate from β5t-expressing progenitor cells. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Proceedings of the National Academy of Sciences of the United States of America 0027-8424 110 24 9885 9890 20130600 10.1073/pnas.1301799110 23720310 soutaro/published_papers/25858464 Enkhsaikhan Lkhagvasuren Lkhagvasuren E Mie Sakata Sakata M Izumi Ohigashi Ohigashi I Yousuke Takahama Takahama Y Lymphotoxin beta Receptor Regulates the Development of CCL21-Expressing Subset of Postnatal Medullary Thymic Epithelial Cells Lymphotoxin β receptor regulates the development of CCL21-expressing subset of postnatal medullary thymic epithelial cells. JOURNAL OF IMMUNOLOGY Journal of immunology (Baltimore, Md. : 1950) 0022-1767 190 10 5110 5117 20130500 10.4049/jimmunol.1203203 23585674 soutaro/published_papers/25861838 Nitta T Ohigashi I Takahama Y The development of T lymphocytes in fetal thymus organ culture. Humana Press Methods in molecular biology (Clifton, N.J.) 1940-6029 946 85 102 20130000 10.1007/978-1-62703-128-8_6 23179827 soutaro/published_papers/25861836 Yasushi Nakagawa Nakagawa Y Izumi Ohigashi Ohigashi I Takeshi Nitta Nitta T Mie Sakata Sakata M Keiji Tanaka Tanaka K Shigeo Murata Murata S Osami Kanagawa Kanagawa O Yousuke Takahama Takahama Y Thymic nurse cells provide microenvironment for secondary T cell receptor alpha rearrangement in cortical thymocytes Thymic nurse cells provide microenvironment for secondary T cell receptor α rearrangement in cortical thymocytes. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Proceedings of the National Academy of Sciences of the United States of America 0027-8424 109 50 20572 20577 20121200 10.1073/pnas.1213069109 23188800 soutaro/published_papers/25861842 Natalie A. Roberts Roberts NA Andrea J. White White AJ William E. Jenkinson Jenkinson WE Gleb Turchinovich Turchinovich G Kyoko Nakamura Nakamura K David R. Withers Withers DR Fiona M. McConnell McConnell FM Guillaume E. Desanti Desanti GE Cecile Benezech Benezech C Sonia M. Parnell Parnell SM Adam F. Cunningham Cunningham AF Magdalena Paolino Paolino M Josef M. Penninger Penninger JM Anna Katharina Simon Simon AK Takeshi Nitta Nitta T Izumi Ohigashi Ohigashi I Yousuke Takahama Takahama Y Jorge H. Caamano Caamano JH Adrian C. Hayday Hayday AC Peter J. L. Lane Lane PJ Eric J. Jenkinson Jenkinson EJ Graham Anderson Anderson G Rank Signaling Links the Development of Invariant gamma delta T Cell Progenitors and Aire(+) Medullary Epithelium Rank signaling links the development of invariant γδ T cell progenitors and Aire(+) medullary epithelium. IMMUNITY Immunity 1074-7613 36 3 427 437 20120300 10.1016/j.immuni.2012.01.016 22425250 soutaro/published_papers/25861844 Izumi Ohigashi Takeshi Nitta Enkhsaikhan Lkhagvasuren Hisataka Yasuda Yousuke Takahama Effects of RANKL on the thymic medulla EUROPEAN JOURNAL OF IMMUNOLOGY 0014-2980 41 7 1822 1827 20110700 10.1002/eji.201141480 21706487 soutaro/published_papers/25861846 Takeshi Nitta Izumi Ohigashi Yasushi Nakagawa Yousuke Takahama Cytokine crosstalk for thymic medulla formation CURRENT OPINION IN IMMUNOLOGY 0952-7915 23 2 190 197 20110400 10.1016/j.coi.2010.12.002 21194915 soutaro/published_papers/14796698 Yu Lei Adiratna Mat Ripen Naozumi Ishimaru Izumi Ohigashi Takashi Nagasawa Lukas T. Jeker Michael R. Bösl Georg A. Holländer Yoshio Hayashi Rene De Waal Malefyt Takeshi Nitta Yousuke Takahama Aire-dependent production of XCL1 mediates medullary accumulation of thymic dendritic cells and contributes to regulatory T cell development Journal of Experimental Medicine 0022-1007 208 2 383 394 20110214 10.1084/jem.20102327 21300913 2-s2.0-79951715831 soutaro/published_papers/14796700 Izumi Ohigashi Yuki Yamasaki Tsukasa Hirashima Yousuke Takahama Identification of the Transgenic Integration Site in Immunodeficient tg epsilon 26 Human CD3 epsilon Transgenic Mice PLOS ONE 1932-6203 5 12 e14391 e14391 20101200 10.1371/journal.pone.0014391 21203507 soutaro/published_papers/14796701 N. Matsui S. Nakane F. Saito I. Ohigashi Y. Nakagawa H. Kurobe H. Takizawa T. Mitsui K. Kondo T. Kitagawa Y. Takahama R. Kaji Undiminished regulatory T cells in the thymus of patients with myasthenia gravis Lippincott Williams and Wilkins Neurology 1526-632X 74 10 816 820 20100000 10.1212/WNL.0b013e3181d31e47 20211905 2-s2.0-77949388453 soutaro/published_papers/14796702 Dil Afroz Sultana Shuhei Tomita Michito Hamada Yasuyuki Iwanaga Yuki Kitahama Nguyen Van Khang Shuichi Hirai Izumi Ohigashi Sachiko Nitta Takashi Amagai Satoru Takahashi Yousuke Takahama Gene expression profile of the third pharyngeal pouch reveals role of mesenchymal MafB in embryonic thymus development Blood 0006-4971 113 13 2976 2987 20090326 10.1182/blood-2008-06-164921 19164599 2-s2.0-63849090193 soutaro/published_papers/14796703 Yu Hikosaka Takeshi Nitta Izumi Ohigashi Kouta Yano Naozumi Ishimaru Yoshio Hayashi Mitsuru Matsumoto Koichi Matsuo Josef M Penninger Hiroshi Takayanagi Yoshifumi Yokota Hisakata Yamada Yasunobu Yoshikai Jun-ichiro Inoue Taishin Akiyama Yousuke Takahama The cytokine RANKL produced by positively selected thymocytes fosters medullary thymic epithelial cells that express autoimmune regulator. The thymic medulla provides a microenvironment where medullary thymic epithelial cells (mTECs) express autoimmune regulator and diverse tissue-restricted genes, contributing to launching self-tolerance. Positive selection is essential for thymic medulla formation via a previously unknown mechanism. Here we show that the cytokine RANK ligand (RANKL) was produced by positively selected thymocytes and regulated the cellularity of mTEC by interacting with RANK and osteoprotegerin. Forced expression of RANKL restored thymic medulla in mice lacking positive selection, whereas RANKL perturbation impaired medulla formation. These results indicate that RANKL produced by positively selected thymocytes is responsible for fostering thymic medulla formation, thereby establishing central tolerance. Immunity 1097-4180 29 3 438 450 20080919 10.1016/j.immuni.2008.06.018 18799150 soutaro/published_papers/14796704 Takeshi Nitta Mariam Nasreen Takafumi Seike Atsushi Goji Izumi Ohigashi Tadaaki Miyazaki Tsutomu Ohta Masamoto Kanno Yousuke Takahama IAN family critically regulates survival and development of T lymphocytes Public Library of Science PLoS Biology 1545-7885 4 4 593 605 20060000 10.1371/journal.pbio.0040103 16509771 2-s2.0-33846172748 soutaro/published_papers/14796705 N Mizusawa Noriko Mizusawa T Hasegawa Tomoko Hasegawa Ohigashi, I Izumi Ohigashi C Tanaka-Kosugi Chisato Kosugi N Harada Nagakatsu Harada M Itakura Mitsuo Itakura K Yoshimoto Katsuhiko Yoshimoto Differentiation phenotypes of pancreatic islet beta- and alpha-cells are closely related with homeotic genes and a group of differentially expressed genes Differentiation Penotypes of Pancreatic Islet β- and α-cells are Closely Related with Homeotic Genes and a Group of Differentially Expressed Genes. GENE Gene 0378-1119 331 28 53 63 20040400 10.1016/j.gene.2004.01.016 15094191 soutaro/misc/54266805 Anderson G Cosway EJ James KD Ohigashi I Takahama Y Generation and repair of thymic epithelial cells. In the vertebrate immune system, thymus stromal microenvironments support the generation of αβT cells from immature thymocytes. Thymic epithelial cells are of particular importance, and the generation of cortical and medullary epithelial lineages from progenitor stages controls the initiation and maintenance of thymus function. Here, we discuss the developmental pathways that regulate thymic epithelial cell diversity during both the embryonic and postnatal periods. We also examine how thymus microenvironments respond to injury, with particular focus on mechanisms that ensure regeneration of thymic epithelial cells for the restoration of thymus function. Rockefeller University Press The Journal of Experimental Medicine 1540-9538 221 10 null null 20240912 10.1084/jem.2023089409042024c 39264842 soutaro/misc/25201785 大東 いずみ 石丸 直澄 片貝 智哉 高浜 洋介 T細胞の自己寛容性確立におけるCCL21の役割 生命科学系学会合同年次大会運営事務局 生命科学系学会合同年次大会 2017 [4P2T24 06(3P 20171200 soutaro/misc/28030720 Yousuke Takahama Izumi Ohigashi Song Baik Graham Anderson Generation of diversity in thymic epithelial cells NATURE REVIEWS IMMUNOLOGY 1474-1741 17 5 295 305 20170500 10.1038/nri.2017.12 soutaro/misc/28008474 Muhammad Myn Uddin Izumi Ohigashi Yousuke Takahama Foxn1-beta 5t transcriptional axis controls CD8+T cell production in the thymus JOURNAL OF IMMUNOLOGY 1550-6606 198 1 null null 20170500 soutaro/misc/11275136 Yousuke Takahama Izumi Ohigashi Song Baik Graham Anderson Generation of diversity in thymic epithelial cells Nature Publishing Group Nature Reviews Immunology 1474-1741 17 5 295 305 20170501 10.1038/nri.2017.12 28317923 2-s2.0-85015695119 soutaro/misc/28130146 Izumi Ohigashi Mina Kozai Yousuke Takahama Development and developmental potential of cortical thymic epithelial cells IMMUNOLOGICAL REVIEWS 1600-065X 271 1 10 22 20160500 10.1111/imr.12404 soutaro/misc/11275137 Izumi Ohigashi 大東 いずみ Yousuke Takahama 高浜 洋介 T細胞の自己寛容を確立する胸腺髄質微小環境 自己免疫疾患の発症機構と治療 実験医学増刊号 30 36 20150000 soutaro/misc/28047406 Izumi Ohigashi Yousuke Takahama CCRL1 marks heterogeneity in cortical and medullary thymic epithelial cells EUROPEAN JOURNAL OF IMMUNOLOGY 1521-4141 44 10 2872 2875 20141000 10.1002/eji.201445091 soutaro/misc/28107038 Nuno L. Alves Yousuke Takahama Izumi Ohigashi Ana R. Ribeiro Song Baik Graham Anderson William E. Jenkinson Serial progression of cortical and medullary thymic epithelial microenvironments (vol 44, pg 16, 2014) EUROPEAN JOURNAL OF IMMUNOLOGY 1521-4141 44 7 2197 2197 20140700 soutaro/misc/28041219 Nuno L. Alves Yousuke Takahama Izumi Ohigashi Ana R. Ribeiro Song Baik Graham Anderson William E. Jenkinson Serial progression of cortical and medullary thymic epithelial microenvironments EUROPEAN JOURNAL OF IMMUNOLOGY 1521-4141 44 1 16 22 20140100 soutaro/misc/28630326 Naoko Matsui Izumi Ohigashi Kazuya Kondo Yoshiko Nomura Yousuke Takahama Ryuji Kaji Increased Hassall's corpuscles in myasthenia gravis Patients carrying thymic hyperplasia JOURNAL OF NEUROIMMUNOLOGY 0165-5728 253 1-2 30 31 20121200 soutaro/misc/11275139 Izumi Ohigashi 大東 いずみ Yousuke Takahama 高浜 洋介 Thymic cortical epithelial cells specific expression of thymoproteasome 胸腺プロテアソームの胸腺皮質上皮細胞特異的発現 科学評論社 Clinical immunology & allergology 臨床免疫・アレルギー科 1881-1930 56 3 232 237 20110900 soutaro/misc/11275138 Izumi Ohigashi 大東 いずみ Yousuke Takahama 高浜 洋介 XCL1と胸腺におけるnTregの生成 Infection, Inflammation & Immunity 感染・炎症・免疫 0387-1010 41 60 62 20110000 soutaro/misc/25106954 Hirotsugu Kurobe Cunlan Liu Tomoo Ueno Fumi Saito Izumi Ohigashi Natalie Seach Rieko Arakaki Yoshio Hayashi Tetsuya Kitagawa Martin Lipp Richard L. Boyd Yousuke Takahama CCR7-dependent cortex-to-medulla migration of positively selected thymocytes is essential for establishing central tolerance Immunity 1074-7613 24 2 165 177 20060200 10.1016/j.immuni.2005.12.011 16473829 2-s2.0-32244432265 Izumi Ohigashi 大東 いずみ Tokushima University 徳島大学 若手研究者学長表彰受賞 胸腺上皮細胞亜集団の分化・分岐機構の研究 20131107