Article
Immunology
Maria Jesus Garcia-Leon, Marta Mosquera, Carmela Cela, Juan Alcain, Saulius Zuklys, Georg Hollander, Maria L. Toribio
Summary: Notch signaling plays a crucial role in fate determination and development of thymus-seeding progenitors along the T-cell lineage. It is not only activated in fetal thymic epithelial cells (TECs), but also induced in postnatal cortical and medullary TECs with age. Disruption of Notch signaling leads to reduced medullary region and accelerated degeneration of medullary TECs.
FRONTIERS IN IMMUNOLOGY
(2022)
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)
Article
Immunology
Hanchao Gao, Mengtao Cao, Kai Deng, Yang Yang, Jinqi Song, Ming Ni, Chuntao Xie, Wenna Fan, Chunpei Ou, Dinggen Huang, Lizhong Lin, Lixia Liu, Yangyang Li, Huimin Sun, Xinyu Cheng, Jinmei Wu, Cuilan Xia, Xuefeng Deng, Lisha Mou, Pengfei Chen
Summary: The study utilized single-cell transcriptome analysis to reveal the transcriptional heterogeneity and cellular state evolution during thymic epithelial cell development, identifying the molecular nature and differentiation dynamics of TECs, as well as a population of mTECs expressing adult stem cell markers.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Nanami Mino, Ryunosuke Muro, Ayami Ota, Sachiko Nitta, Veronique Lefebvre, Takeshi Nitta, Keishi Fujio, Hiroshi Takayanagi
Summary: mTECs shape the thymic microenvironment by expressing TRAs, leading to T-cell development. Sox4 is crucial for the development of thymic tuft cells, showing a potential role in diversifying antigen expression within the thymic medulla.
INTERNATIONAL IMMUNOLOGY
(2022)
Article
Cell Biology
Pedro M. Rodrigues, Laura G. Sousa, Chiara Perrod, Ana R. Maceiras, Pedro Ferreirinha, Rita Pombinho, Gema Romera-Cardenas, Maria Gomez-Lazaro, Meryem Senkara, Jelena Pistolic, Didier Cabanes, Ludger Klein, Paul Saftig, Nuno L. Alves
Summary: Thymic epithelial cells (TECs) are crucial for T cell development. This study reveals that lysosomal-associated membrane protein 2 (LAMP2) is highly expressed in cortical TECs (cTECs) and plays a role in autophagy and lysosomal processes. Genetic inactivation of Lamp2 in cTECs impairs the development of CD4 T cells without directing MHC II-restricted cells into the CD8 lineage. The findings suggest that LAMP2 is important for the generation of selecting self-peptides:MHC II complexes in cTECs.
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)
Review
Immunology
Helen Wang, Juan Carlos Zuniga-Pfluecker
Summary: This article highlights the importance of the thymus in T cell development and its interactions with other cell types. The crucial steps of positive and negative selection in generating functional T cells and limiting auto-reactive T cells are discussed. Additionally, the roles of dendritic cells and macrophages in positive and negative selection, as well as their contribution to thymus homeostasis and T cell development, are examined.
FRONTIERS IN IMMUNOLOGY
(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
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)
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
Katrina L. Randall, Hsei Di Law, Andrew F. Ziolkowski, Rushika C. Wirasinha, Christopher C. Goodnow, Stephen R. Daley
Summary: DOCK8 deficiency impairs T-REG development in the thymus without compromising thymocyte deletion.
CLINICAL & TRANSLATIONAL 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
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
Esther Bernaldo-de-Quiros, Beatriz Cozar, Rocio Lopez-Esteban, Maribel Clemente, Juan Miguel Gil-Jaurena, Carlos Pardo, Ana Pita, Ramon Perez-Caballero, Manuela Camino, Nuria Gil, Maria Eugenia Fernandez-Santos, Susana Suarez, Marjorie Pion, Marta Martinez-Bonet, Rafael Correa-Rocha
Summary: Regulatory T cells (Treg) are a promising therapy for controlling inflammation. Umbilical cord blood and discarded pediatric thymus have been proposed as alternative sources of Treg. A novel manufacturing protocol has been developed to obtain high-quality and high-quantity Treg from pediatric thymus, which shows potential for cellular therapy.
FRONTIERS IN 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)
Review
Endocrinology & Metabolism
Nobuyuki Udagawa, Masanori Koide, Midori Nakamura, Yuko Nakamichi, Teruhito Yamashita, Shunsuke Uehara, Yasuhiro Kobayashi, Yuriko Furuya, Hisataka Yasuda, Chie Fukuda, Eisuke Tsuda
Summary: Osteoclasts and osteoblasts play essential roles in bone remodeling, with the regulation of RANKL and OPG expression being a key mechanism. The balance between these factors is crucial for maintaining bone density and preventing bone loss.
JOURNAL OF BONE AND MINERAL METABOLISM
(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
Biochemistry & Molecular Biology
Yuriko Furuya, Hisashi Mera, Maki Itokazu, Shozaburo Terai, Hiroaki Nakamura, Shigeyuki Wakitani, Hisataka Yasuda
Summary: W9 has been found to stimulate the proliferation and differentiation of chondrocytes, promoting the repair of articular cartilage defects. By increasing the volume of cartilaginous matrices and inducing the proliferation and differentiation of chondrocytes, W9 has the potential to address the unmet medical needs for treating cartilage damage.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
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)
Article
Endocrinology & Metabolism
Masanori Koide, Teruhito Yamashita, Keigo Nakamura, Hisataka Yasuda, Nobuyuki Udagawa, Yasuhiro Kobayashi
Summary: This study found that approximately two-thirds of bone formation is remodeling-based in Sost-deficient mice, while remodeling-based bone formation accounts for most of the bone formation in Sost(+/-) mice. Anti-RANKL antibody may be useful for detecting modeling-based bone formation on trabecular bone.
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)
