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en: Thymus research in relation to myasthenia gravis : a new perspective on cell subpopulations and future directions

en: 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.

en: Frontiers in Immunology

ja: Frontiers in Immunology


en: Generation and repair of thymic epithelial cells

en: 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.

en: The Journal of Experimental Medicine

ja: The Journal of Experimental Medicine


en: Tissue-specific proteasomes in generation of MHC class I peptides and CD8+ T cells

en: 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.

en: Current Opinion in Immunology

ja: Current Opinion in Immunology


en: Thymoproteasome optimizes positive selection of CD8+ T cells without contribution of negative selection

en: Advances in Immunology

ja: Advances in Immunology


en: The role of proteasomes in the thymus

ja: The role of proteasomes in the thymus


en: Generation of diversity in thymic epithelial cells

en: In the thymus, diverse populations of thymic epithelial cells (TECs), including cortical and medullary TECs and their subpopulations, have distinct roles in coordinating the development and repertoire selection of functionally competent and self-tolerant T cells. Here, we review the expanding diversity in TEC subpopulations in relation to their functions in T cell development and selection as well as their origins and development.

en: Nature Reviews. Immunology

ja: Nature Reviews. Immunology


en: T細胞の自己寛容を確立する胸腺髄質微小環境

ja: T細胞の自己寛容を確立する胸腺髄質微小環境

en: 自己免疫疾患の発症機構と治療 実験医学増刊号

ja: 自己免疫疾患の発症機構と治療 実験医学増刊号


en: XCL1と胸腺におけるnTregの生成

ja: XCL1と胸腺におけるnTregの生成

en: Infection, Inflammation & Immunity

ja: 感染·炎症·免疫


en: Thymic cortical epithelial cells specific expression of thymoproteasome

ja: 胸腺プロテアソームの胸腺皮質上皮細胞特異的発現

en: Clinical Immunology & Allergology

ja: 臨床免疫·アレルギー科