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)
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
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
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
Oncology
Huiyang Li, Bo Ren, Shili Yu, Hongwen Gao, Ping-Li Sun
Summary: This study investigated the expression of six novel thymic epithelial markers in thymic tumors and explored their correlation with histological classification, Masaoka-Koga stage, and prognosis. The results demonstrated that these markers could be used as ancillary markers in the diagnosis and prognosis of thymic epithelial tumors.
Review
Immunology
Honyin Chiu, Peter S. Linsley, Steven F. Ziegler
Summary: The thymus is a complex organ composed of various thymic epithelial cells (TECs) that play different roles in the development and selection of T cells. Recent advancements in technologies like single-cell RNA sequencing have allowed for the investigation of TEC heterogeneity and provided insights into the molecular mechanisms regulating TEC function and antigen expression. This review focuses on the newly characterized subsets of TECs and their diversity in supporting T cell development, as well as recent discoveries in self-antigen expression during TEC development and thymic involution.
JOURNAL OF IMMUNOLOGY
(2023)
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)
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
Xue Dong, Zhanfeng Liang, Jiayu Zhang, Qian Zhang, Yanan Xu, Zhaoqi Zhang, Lianfeng Zhang, Baojun Zhang, Yong Zhao
Summary: This study investigates the role of transport protein particle complexes (Trappcs) in the development and maturation of thymic epithelial cells (TECs). The researchers find that Trappc1 deficiency leads to severe thymic atrophy, decreased TEC cell numbers, and impaired TEC maturation. Additionally, TEC-specific Trappc1 deletion results in poor thymic T cell output and increased activation of memory T cells, contributing to spontaneous autoimmune disorders. Molecular studies reveal that reduced endoplasmic reticulum and Golgi apparatus, enhanced unfolded protein response, apoptosis, and reactive oxygen species generation are involved in the reduction of Trappc1-deleted TECs.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2022)
Review
Immunology
Takeshi Nitta, Ayami Ota, Takahiro Iguchi, Ryunosuke Muro, Hiroshi Takayanagi
Summary: Fibroblasts in the thymus play important roles in thymus organogenesis and immune responses, but their immunological significance has not been fully elucidated. New technologies such as multicolor flow cytometry and single cell-based transcriptome profiling help us better understand the development and functions of thymic fibroblasts.
IMMUNOLOGICAL REVIEWS
(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)
Article
Immunology
Claudia Haftmann, Pascale Zwicky, Florian Ingelfinger, Florian Mair, Stefan Floess, Rene Riedel, Pawel Durek, Marianne R. Spalinger, Ekaterina Friebel, Brian P. Leung, Mirjam Lutz, Nicole Puertas, Ana Amorim, Stefanie Scharli, Benedict Becher, Jan Kisielow, Ari Waisman, Mir-Farzin Mashreghi, Jochen Huehn, Burkhard Becher
Summary: Medullary thymic epithelial cells (mTECs) play a crucial role in regulating T cell immune tolerance by negatively selecting self-reactive T cells and promoting the development of regulatory T cells. Dysfunctional regulatory T cells may be a key factor in the development of autoimmune diseases.
SCIENCE IMMUNOLOGY
(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
Multidisciplinary Sciences
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
NATURE COMMUNICATIONS
(2020)
Review
Immunology
Jennifer E. Cowan, Yousuke Takahama, Avinash Bhandoola, Izumi Ohigashi
FRONTIERS IN IMMUNOLOGY
(2020)
Article
Multidisciplinary Sciences
Norimasa Iwanami, Kohei Takeshita, Divine-Fondzenyuy Lawir, Isao Suetake, Shoji Tajima, Katarzyna Sikora, Ines Trancoso, Connor OMeara, Iliana Siamishi, Yousuke Takahama, Makoto Furutani-Seiki, Hisato Kondoh, Yasushige Yonezawa, Michael Schorpp, Thomas Boehm
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
Hematology
Kieran D. James, Daniel F. Legler, Vladimir Purvanov, Izumi Ohigashi, Yousuke Takahama, Sonia M. Parnell, Andrea J. White, William E. Jenkinson, Graham Anderson
Summary: The release of newly selected alpha beta T cells from the thymus is crucial for establishing a functional adaptive immune system, particularly the emigration of the first cohorts of cells during the neonatal period. The study demonstrated the importance of CCL21 in neonatal thymus emigration, highlighting its role in the initial formation of the peripheral immune system. Additionally, an intrathymic mechanism involving cell-specific production and presentation of CCL21 was identified, showing a functional synergy between thymic epithelial and mesenchymal cells in alpha beta T-cell emigration.
Article
Immunology
Izumi Ohigashi, Melina Frantzeskakis, Alison Jacques, Sayumi Fujimori, Aya Ushio, Fusano Yamashita, Naozumi Ishimaru, Da Yin, Margaret Cam, Michael C. Kelly, Parirokh Awasthi, Kensuke Takada, Yousuke Takahama
Summary: The study revealed that the thymoproteasome plays a crucial role in the production of CD8(+) T cells, optimizing the cell development process. This finding indicates that the thymoproteasome regulates the formation of the TCR repertoire, playing a key role in the development of CD8(+) T cells.
JOURNAL OF EXPERIMENTAL MEDICINE
(2021)
Article
Multidisciplinary Sciences
Daiki Hashimoto, Jose Gabriel R. Colet, Aki Murashima, Kota Fujimoto, Yuko Ueda, Kentaro Suzuki, Taiju Hyuga, Hiroaki Hemmi, Tsuneyasu Kaisho, Satoru Takahashi, Yousuke Takahama, Gen Yamada
Summary: The thymus facilitates mature T cell production through stromal microenvironment, which can be impaired by radiation and aging. MafB, a transcription factor in thymic stroma, plays important roles in thymic regeneration and its absence may impede thymic recovery and accelerate age-related thymic involution.
SCIENTIFIC REPORTS
(2021)
Review
Immunology
Melina Frantzeskakis, Yousuke Takahama, Izumi Ohigashi
Summary: The thymus provides a microenvironment for T cell generation and selection, with cTECs expressing thymoproteasomes for optimal CD8(+) T cell positive selection, and mTECs expressing immunoproteasomes for self-tolerance in T cells.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Cell Biology
Izumi Ohigashi, Yousuke Takahama
Summary: Beta 5t has a specific impact on proteasome subunit composition in cTECs, contributing to the optimization of CD8(+) T cell development through the production of unique self-peptides associated with MHC-I. However, controversy exists regarding the role of beta 5t in regulating cTEC gene expression and inducing oxidative stress in thymocytes.
Editorial Material
Immunology
Yousuke Takahama
Summary: The study suggests that prolonged damage in thymic medullary epithelial cells may lead to failure in self-tolerance in newly generated T cells and provoke post-transplant autoimmunity.
JOURNAL OF EXPERIMENTAL MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Izumi Ohigashi, Mami Matsuda-Lennikov, Yousuke Takahama
Summary: MHC-associated peptides displayed by antigen-presenting cells in the thymus play a crucial role in the generation of self-tolerant T cells that protect the body from pathogens. Different types of thymic epithelial cells, such as cTECs and mTECs, are involved in the selection process of T cells to establish self-tolerance.
Article
Biology
Sayumi Fujimori, Izumi Ohigashi, Hayato Abe, Yosuke Matsushita, Toyomasa Katagiri, Makoto M. Taketo, Yousuke Takahama, Shinji Takada
Summary: The thymic epithelium plays a crucial role in supporting the development of T cells. This study found that enhanced expression of beta-catenin in thymic epithelial cells leads to thymic dysplasia and T cell deficiency in the embryonic period, while loss of beta-catenin function only slightly reduces cortical thymic epithelial cells and thymocytes in postnatal development.
Article
Multidisciplinary Sciences
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
Summary: This study demonstrates that memory B cells can recycle back to germinal centers via CCL-21 mediated chemotaxis to transport antigens, potentially contributing to affinity maturation and antigenic drift.
NATURE COMMUNICATIONS
(2022)
Review
Immunology
Mami Matsuda-Lennikov, Izumi Ohigashi, Yousuke Takahama
Summary: Thymoproteasomes and immunoproteasomes are two types of tissue-specific proteasomes that play important roles in the development of CD8(+) T cells.
CURRENT OPINION IN IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Beth Lucas, Andrea J. White, Fabian Klein, Clara Veiga-Villauriz, Adam Handel, Andrea Bacon, Emilie J. Cosway, Kieran D. James, Sonia M. Parnell, Izumi Ohigashi, Yousuke Takahama, William E. Jenkinson, Georg A. Hollander, Wei-Yu Lu, Graham Anderson
Summary: Although the importance of thymic epithelial cells (TEC) in thymus physiology is established, the development of functionally diverse TEC populations remains incompletely understood. Here, using fate-mapping experiments in the embryonic thymus, the authors identify keratin19(+) multipotent progenitor cells that support medullary TEC diversity in adulthood.
NATURE COMMUNICATIONS
(2023)
