Article
Cell Biology
Qian Zhang, Zhanfeng Liang, Jiayu Zhang, Tong Lei, Xue Dong, Huiting Su, Yifang Chen, Zhaoqi Zhang, Liang Tan, Yong Zhao
Summary: The study reveals the crucial role of the epigenetic regulator Sirt6 in the development and differentiation of mTECs, with its deficiency leading to decreased mTEC compartment, accelerated differentiation, and autoimmune diseases.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biology
Noella Lopes, Nicolas Boucherit, Jeremy C. Santamaria, Nathan Provin, Jonathan Charaix, Pierre Ferrier, Matthieu Giraud, Magali Irla
Summary: Interactions between developing T cells and Aire(+) medullary thymic epithelial cells are crucial for central tolerance induction in the thymus. Self-reactive CD4(+) thymocytes control the transcriptional regulators and composition of mTEC(lo) subsets, including Aire(+) mTEC(hi) precursors, post-Aire and tuft-like mTECs. These interactions upregulate the expression of tissue-restricted self-antigens, cytokines, chemokines, and adhesion molecules important for T-cell development. Our study reveals that self-reactive CD4(+) thymocytes control multiple facets of immature mTECs, determining their heterogeneity.
Article
Immunology
Xue Dong, Jiayu Zhang, Qian Zhang, Zhanfeng Liang, Yanan Xu, Yong Zhao, Baojun Zhang
Summary: Thymic epithelial cells (TECs) play a critical role in the development and function of the immune system. This study demonstrates the importance of Dhx9 protein in the differentiation and function of mTECs, and its deficiency leads to decreased TEC cell numbers and the development of spontaneous autoimmune disorders.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Immunology
Manpreet K. Semwal, Nicholas E. Jones, Ann V. Griffith
Summary: The thymus is crucial for T lymphocyte development, with thymic stromal cells playing an important role. Metabolic regulation of thymic stromal cell function is an emerging area of study.
FRONTIERS IN IMMUNOLOGY
(2021)
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
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
Francesca Ferrua, Ileana Bortolomai, Elena Fontana, Dario Di Silvestre, Rosita Rigoni, Genni Enza Marcovecchio, Elena Draghici, Francesca Brambilla, Maria Carmina Castiello, Gloria Delfanti, Despina Moshous, Capucine Picard, Tom Taghon, Victoria Bordon, Ansgar S. Schulz, Catharina Schuetz, Silvia Giliani, Annarosa Soresina, Andrew R. Gennery, Sara Signa, Blachy J. Davila Saldana, Ottavia M. Delmonte, Luigi D. Notarangelo, Chaim M. Roifman, Pietro Luigi Poliani, Paolo Uva, Pier Luigi Mauri, Anna Villa, Marita Bosticardo
Summary: MHCII deficiency, also known as Bare Lymphocyte Syndrome, is a rare combined immunodeficiency resulting in impaired immune responses and susceptibility to infections and autoimmunity. Studies have shown abnormalities in thymic structure and function in both patients and mice with MHCII deficiency, likely due to impaired mTEC maturation and gene expression. This disease-specific TEC defects contribute to perturbation of central tolerance and pose challenges for potential benefits of hematopoietic stem cell transplantation.
FRONTIERS IN IMMUNOLOGY
(2021)
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)
Review
Immunology
Jayashree Srinivasan, Jessica N. Lancaster, Nandini Singarapu, Laura P. Hale, Lauren I. R. Ehrlich, Ellen R. Richie
Summary: Thymic epithelial cells and hematopoietic antigen presenting cells play essential roles in central tolerance, inducing negative selection or generation of regulatory T cells. Changes in TEC and HAPC subsets across the lifespan may have potential consequences for central tolerance. Age-associated alterations in T cell and Treg function relate to changes in thymic HAPC and TEC subsets.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Manpreet K. Semwal, Allison K. Hester, Yangming Xiao, Chioma Udeaja, Sergio Cepeda, John S. Verschelde, Nicholas Jones, Sarah A. Wedemeyer, Simon Emtage, Kymberly Wimberly, Ann V. Griffith
Summary: This study reveals that constitutive autophagy in TSCs is regulated by low expression of catalase, which affects central T cell tolerance and may be associated with the development of autoimmune diseases.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Immunology
Nathan Provin, Matthieu Giraud
Summary: The thymus plays a crucial role in immune tolerance, but genetic disorders can lead to thymic dysfunction and autoimmune syndromes. Recent advances in gene editing and pluripotent stem cell differentiation offer new possibilities for studying and treating genetic pathologies affecting the thymus.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Immunology
Ruben G. R. Pinheiro, Nuno L. Alves
Summary: TECs play an essential role in the formation of functionally diverse and self-tolerant T cells, particularly in the first weeks after birth in mice. Recent studies highlight the critical coordination between the expansion and maturation of TECs during this period and their specialized role in T cell development and selection. The impact of aging on TEC progenitors and maintenance of functional thymic epithelial microenvironments is discussed, along with how these changes affect the thymus's ability to sustain regular thymopoiesis throughout life.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Cell Biology
Jessica N. Lancaster, Damaris E. Keatinge-Clay, Jayashree Srinivasan, Yu Li, Hilary J. Selden, Seohee Nam, Ellen R. Richie, Lauren I. R. Ehrlich
Summary: Thymus involution in immune aging reduces the number of newly generated T cells and alters the thymus microenvironment. The middle-aged thymic environment does not support efficient motility of medullary thymocytes, leading to impaired central tolerance against moderate-avidity self-antigens and a decrease in Treg cells.
Article
Immunology
Kenta Horie, Kano Namiki, Kyouhei Kinoshita, Maki Miyauchi, Tatsuya Ishikawa, Mio Hayama, Yuya Maruyama, Naho Hagiwara, Takahisa Miyao, Shigeo Murata, Tetsuya J. Kobayashi, Nobuko Akiyama, Taishin Akiyama
Summary: The thymus has the ability to regenerate from acute injuries, but these injuries can affect the heterogeneity and gene expression of thymic epithelial cells for an extended period, potentially impairing thymic T cell selection.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Jiayi Dong, Lindsey M. Warner, Ling-Li Lin, Mei-Chi Chen, Ryan M. O'Connell, Li-Fan Lu
Summary: miR-155 plays a crucial role in promoting tT reg cell differentiation by promoting mTEC maturation in the thymus. RANKL stimulation induces miR-155 expression to target molecules within the TGF beta signaling pathway, safeguarding thymic medulla integrity.
JOURNAL OF EXPERIMENTAL MEDICINE
(2021)
Article
Geriatrics & Gerontology
Toshihiro Higashikawa, Yuko Hamazaki, Osamu Iritani, Takuro Morita, Taroh Himeno, Tazuo Okuno, Hiroshi Yano, Keisuke Watanabe, Masashi Okuro, Tsugiyasu Kanda, Shigeto Morimoto
GERIATRICS & GERONTOLOGY INTERNATIONAL
(2016)
Article
Cardiac & Cardiovascular Systems
Yoriyasu Suzuki, Etsuo Tsuchikane, Osamu Katoh, Toshiya Muramatsu, Makoto Muto, Koichi Kishi, Yuji Hamazaki, Yuji Oikawa, Tomohiro Kawasaki, Atsunori Okamura
JACC-CARDIOVASCULAR INTERVENTIONS
(2017)
Article
Immunology
Kyosuke Sato, Aiko Kato, Miho Sekai, Yoko Hamazaki, Nagahiro Minato
JOURNAL OF IMMUNOLOGY
(2017)
Article
Multidisciplinary Sciences
Koyu Ito, Akira Nakajima, Yuji Fukushima, Keiichiro Suzuki, Keiko Sakamoto, Yoko Hamazaki, Kouetsu Ogasawara, Nagahiro Minato, Masakazu Hattori
Article
Oncology
Tomoharu Sugie, Eiji Suzuki, Akira Yamauchi, Kazuhiko Yamagami, Norikazu Masuda, Naomi Gondo, Eriko Sumi, Takafumi Ikeda, Harue Tada, Ryuji Uozumi, Shotaro Kanao, Yoshimasa Tanaka, Yoko Hamazaki, Nagahiro Minato, Masakazu Toi
Correction
Cell Biology
Takeshi Ito, Yoko Hamazaki, Akifumi Takaori-Kondo, Nagahiro Minato
CELL STRUCTURE AND FUNCTION
(2018)
Article
Geriatrics & Gerontology
Koshiro Sakai, Shinji Koba, Yuya Nakamura, Yuya Yokota, Fumiyoshi Tsunoda, Makoto Shoji, Yasuki Itoh, Yuji Hamazaki, Youichi Kobayashi
GERIATRICS & GERONTOLOGY INTERNATIONAL
(2018)
Article
Cardiac & Cardiovascular Systems
Ryota Kosaki, Yoshino Minoura, Kunihiro Ogura, Yosuke Oishi, Lisa Tanaka, Ken Arai, Kosuke Nomura, Koshiro Sakai, Teruo Sekimoto, Tenjin Nisikura, Hiroaki Tsujita, Seita Kondo, Shigeto Tsukamoto, Yuji Hamazaki, Youichi Kobayashi
JOURNAL OF CARDIOLOGY
(2018)
Article
Multidisciplinary Sciences
Hidehiko Suzuki, Takahiro Nagatake, Ayaka Nasu, Huangwenxian Lan, Koji Ikegami, Mitsutoshi Setou, Yoko Hamazaki, Hiroshi Kiyono, Kiyohito Yagi, Masuo Kondoh, Jun Kunisawa
SCIENTIFIC REPORTS
(2018)
Article
Immunology
Aiko Kato, Akifumi Takaori-Kondo, Nagahiro Minato, Yoko Hamazaki
EUROPEAN JOURNAL OF IMMUNOLOGY
(2018)
Article
Immunology
Jianwei Wang, Miho Sekai, Takeshi Matsui, Yosuke Fujii, Mitsuru Matsumoto, Osamu Takeuchi, Nagahiro Minato, Yoko Hamazaki
INTERNATIONAL IMMUNOLOGY
(2019)
Article
Nutrition & Dietetics
Maiko Kato, Yumi Hamazaki, Simo Sun, Yoshikazu Nishikawa, Eriko Kage-Nakadai
Meeting Abstract
Cardiac & Cardiovascular Systems
S. Takeshi, E. T. Tsuchikane, T. M. Muramatsu, K. K. Kishi, M. M. Muto, Y. O. Oikawa, T. K. Kawasaki, T. F. Fujita, Y. H. Hamazaki, H. O. Okada
EUROPEAN HEART JOURNAL
(2018)
Meeting Abstract
Hematology
Yoshinobu Konishi, Kenta Terai, Takaya Abe, Yoko Hamazaki, Akifumi Takaori-Kondo, Michiyuki Matsuda
Article
Medicine, Research & Experimental
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