Article
Multidisciplinary Sciences
Jason A. Carter, Leonie Stroemich, Matthew Peacey, Sarah R. Chapin, Lars Velten, Lars M. Steinmetz, Benedikt Brors, Sheena Pinto, Hannah Meyer
Summary: This study reveals the transcriptomic diversity of mTECs in the thymus and establishes a web portal for querying their transcriptome, which may aid in identifying the drivers of autoimmune diseases.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Daniel A. Michelson, Christophe Benoist, Diane Mathis
Summary: Medullary thymic epithelial cells (mTECs) are crucial for T cell central tolerance. In addition to the transcription factor Aire, we found that mTECs express the inhibitory receptor CTLA-4. CTLA-4(+) mTECs have a distinct gene signature associated with antigen presentation and interferon-gamma signaling, complementing the role of Aire.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Daniel A. Michelson, Koji Hase, Tsuneyasu Kaisho, Christophe Benoist, Diane Mathis
Summary: Medullary thymic epithelial cells (mTECs) ectopically express thousands of peripheral-tissue antigens (PTAs), which drive deletion or phenotypic diversion of self-reactive immature T cells during thymic differentiation. Lineage-defining transcription factors (TFs) for distinct cell types are present in different mTEC subtypes, and these factors are essential for the accumulation of mimetic cells and the expression of PTAs, contributing to self-tolerance.
Article
Immunology
Matthew D. D. Taves, Kaitlynn M. M. Donahue, Jing Bian, Margaret C. C. Cam, Jonathan D. D. Ashwell
Summary: TECs produce glucocorticoids to promote T cell repertoire, and the expression of Cyp11b1, an enzyme involved in glucocorticoid production, is dependent on Aire. Aire not only induces tissue-restricted antigen expression, but also promotes glucocorticoid production, expanding and enhancing the T cell receptor repertoire.
SCIENCE IMMUNOLOGY
(2023)
Review
Immunology
Daniel A. Michelson, Diane Mathis
Summary: Medullary thymic epithelial cells (mTECs) delete or divert autoreactive T cells by expressing peripheral-tissue antigens (PTAs) ectopically. Recently, attention has been refocused on thymic mimetic cells, which play important roles in establishing T cell tolerance and autoimmunity.
TRENDS IN IMMUNOLOGY
(2022)
Article
Oncology
Minoru Matsumoto, Takuya Ohmura, Yuto Hanibuchi, Mayuko Ichimura-Shimizu, Yasuyo Saijo, Hirohisa Ogawa, Ryuichiro Miyazawa, Junko Morimoto, Koichi Tsuneyama, Mitsuru Matsumoto, Takeshi Oya
Summary: Despite the physiological distinction between cTECs and mTECs, the origin of TCs and other thymic epithelial tumors has been unclear. By studying the mTEC-specific transcriptional regulator AIRE, it was found that a significant proportion of TCs express AIRE with characteristic nuclear dot morphology. This expression was supported by RNA-seq data and further analysis revealed that TCs exhibit molecular characteristics of multiple mTEC subpopulations, suggesting their derivation from mTECs.
Review
Immunology
Im-Hong Sun, Eva Gillis-Buck, Tippi C. Mackenzie, James M. Gardner
Summary: This review discusses the importance of maternal immune tolerance to fetal and placental tissues during pregnancy and the role of autoimmune regulator (Aire) in this process. Recent studies have identified various populations of Aire-expressing cells in secondary lymphoid organs, which contribute to the maintenance of maternal-fetal tolerance. Deletion of these cells during pregnancy leads to T-cell activation and lymphocytic infiltration of the uterus, resulting in pregnancy complications.
IMMUNOLOGICAL REVIEWS
(2022)
Article
Multidisciplinary Sciences
Thomas Barthlott, Adam E. Handel, Hong Ying Teh, Rushika C. Wirasinha, Katrin Hafen, Saulius Zuklys, Benoit Roch, Stuart H. Orkin, Jean-Pierre de Villartay, Stephen R. Daley, Georg A. Hollaender
Summary: Thymic T cell development and T cell receptor repertoire selection rely on molecular signals from thymic epithelial cells (TEC), whose development and function are epigenetically regulated. Disruption of PRC2 activity alters H3K27me3 configuration, impairs TEC functions, and affects T cell development.
NATURE COMMUNICATIONS
(2021)
Article
Immunology
Martti Laan, Ahto Salumets, Annabel Klein, Kerli Reintamm, Rudolf Bichele, Hedi Peterson, Part Peterson
Summary: The study provides insights into the role of Aire-positive mTECs in central tolerance induction and the potential contribution of post-Aire mTECs and Hassall's corpuscles to the thymic microenvironment. The analysis suggests a novel mechanism by which late-stage mTECs in humans display a distinct pro-inflammatory signature.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Michael Frech, Heike Danzer, Pooja Uchil, Vugar Azizov, Eva Schmid, Fabian Schalter, Kerstin Durholz, Daniele Mauro, Simon Rauber, Luis Munoz, Leila Taher, Francesco Ciccia, Kilian Schober, Magali Irla, Kerstin Sarter, Georg Schett, Mario M. Zaiss
Summary: Butyrophilin 2a2 (Btn2a2), predominantly expressed by thymic epithelial cells (TEC), inhibits conventional T cell activation and affects thymic T cell maturation and central tolerance mechanisms. Btn2a2-/- mice develop spontaneous autoimmunity resembling human primary Sjögren's Syndrome (pSS), including the formation of tertiary lymphoid structures (TLS) in target organs.
JOURNAL OF AUTOIMMUNITY
(2023)
Article
Multidisciplinary Sciences
Yoshiaki Yasumizu, Naganari Ohkura, Hisashi Murata, Makoto Kinoshita, Soichiro Funaki, Satoshi Nojima, Kansuke Kido, Masaharu Kohara, Daisuke Motooka, Daisuke Okuzaki, Shuji Suganami, Eriko Takeuchi, Yamami Nakamura, Yusuke Takeshima, Masaya Arai, Satoru Tada, Meinoshin Okumura, Eiichi Morii, Yasushi Shintani, Shimon Sakaguchi, Tatsusada Okuno, Hideki Mochizuki
Summary: This study reveals the ectopic expression of neuromuscular molecules in MG-type thymoma, specifically in a distinct subpopulation of medullary thymic epithelial cells (nmTECs). MG-thymoma exhibits microenvironments dedicated to autoantibody production and cell-cell interactions between nmTECs and T/B cells. The findings suggest that nmTECs play a significant role in the pathogenesis of MG through ectopic expression of neuromuscular molecules.
NATURE COMMUNICATIONS
(2022)
Article
Immunology
Hitoshi Nishijima, Minoru Matsumoto, Junko Morimoto, Kazuyoshi Hosomichi, Nobuko Akiyama, Taishin Akiyama, Takeshi Oya, Koichi Tsuneyama, Hideyuki Yoshida, Mitsuru Matsumoto
Summary: The deficiency of Aire leads to autoimmunity, and Aire indirectly induces the expression of TRAs by controlling the heterogeneity of mTECs. Analysis of transcriptomic data from Aire-augmented and Aire-deficient mTECs reveals that many Aire-dependent genes may not be direct transcriptional targets of Aire, while Ccl25 is identified as a canonical target of Aire.
JOURNAL OF IMMUNOLOGY
(2022)
Article
Immunology
Pedro Ferreirinha, Camila Ribeiro, Junko Morimoto, Jonathan J. M. Landry, Minoru Matsumoto, Catarina Meireles, Andrea J. White, Izumi Ohigashi, Leonor Araujo, Vladimir Benes, Yousuke Takahama, Graham Anderson, Mitsuru Matsumoto, Nuno L. Alves
Summary: This study identified a new classification method for the late stages of mTEC differentiation and confirmed the precursor-product relationship between different subsets through transcriptomic analysis of specific genetic programs, providing insights into their characteristics.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Zhanfeng Liang, Zhaoqi Zhang, Qian Zhang, Xue Dong, Xiaofeng Yang, Jiayu Zhang, Tong Lei, John W. M. Creemers, Baojun Zhang, Yong Zhao
Summary: The study revealed that Furin is highly expressed in thymic epithelial cells (TECs) and its deletion leads to reduced TECs, thymic atrophy, impaired thymopoiesis, and autoimmune disorders. Furin promotes TEC development through the cleavage of proproteins and activation of signaling pathways. This study highlights the importance of post-translational modification of immature proproteins in TEC biology.
Article
Immunology
Gustaaf G. van Laar, Jan Piet van Hamburg, Sander W. Tas
Summary: Auto-immune regulator (AIRE) is a transcription factor mainly found in the thymus, but recent studies have identified its expression in other tissues as well. The exact function of these extrathymic AIRE expressing cells (eTACs) is still unknown, but they have the potential to modulate or inhibit immune responses, making them promising targets for restoring tolerance in autoimmune diseases or improving immuno-therapy in cancer settings.
AUTOIMMUNITY REVIEWS
(2022)