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.
Review
Immunology
Takeshi Nitta, Hiroshi Takayanagi
Summary: The stromal microenvironment in the thymus is crucial for generating a functional T cell repertoire, with thymic epithelial cells (TECs) being the most prominent type. Besides TECs, other stromal cell types of mesenchymal origin also play important roles in controlling TEC development. The recently discovered functional effect of thymic fibroblasts on T cell repertoire selection is highlighted as a significant advancement in our understanding of thymic organogenesis and T cell development.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Immunology
Tatsuya Ishikawa, Nobuko Akiyama, Taishin Akiyama
Summary: Peripheral T cells are crucial components of the adaptive immune system, capable of distinguishing between self and non-self antigens. Thymic epithelial cells (TECs) play a key role in orchestrating the development and selection of self-tolerant T cells. Recent studies have uncovered the heterogeneity of TECs, but the identity of adult thymic TEC progenitors remains unclear.
FRONTIERS IN IMMUNOLOGY
(2021)
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
Allergy
Rafael Gras-Pena, Nichole M. Danzl, Mohsen Khosravi-Maharlooei, Sean R. Campbell, Amanda E. Ruiz, Christopher A. Parks, William Meng Suen Savage, Markus A. Holzl, Debanjana Chatterjee, Megan Sykes
Summary: This study developed a novel differentiation protocol to generate human thymic epithelial progenitors from human embryonic stem cells (hES-TEPs) and demonstrated their thymopoietic function in vivo. By incorporating hES-TEPs into a supportive thymic structure, the researchers enhanced human thymocyte development and increased the reconstitution of peripheral CD4+ naive T cells.
JOURNAL OF ALLERGY AND CLINICAL 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
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
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
Endocrinology & Metabolism
Soo Hyun Ahn, Sean L. Nguyen, Tae Hoon Kim, Jae-Wook Jeong, Ripla Arora, John P. Lydon, Margaret G. Petroff
Summary: Progesterone is a crucial hormone for the success of pregnancy, specifically in the female reproductive organs. It prepares the endometrium for embryo implantation and plays a role in thymic involution during pregnancy.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Review
Oncology
Cexun Hu, Keyu Zhang, Feng Jiang, Hui Wang, Qixiang Shao
Summary: The thymus degenerates as humans age, leading to decreased immune response and higher susceptibility to autoimmune diseases. Epigenetics play a crucial role in regulating the development and senescence of thymic epithelial cells, offering potential therapeutic strategies for thymus atrophy.
CLINICAL EPIGENETICS
(2021)
Article
Biology
Matous Voboril, Jiri Brezina, Tomas Brabec, Jan Dobes, Ondrej Ballek, Martina Dobesova, Jasper Manning, Richard S. Blumberg, Dominik Filipp
Summary: mTECs and DCs in the thymus work together to present self-antigens derived from medullary thymic epithelial cells, which is essential for central tolerance. Research has shown that different subsets of thymic DCs selectively target distinct subsets of mTECs, with XCR1(+) activated DC subset being the most potent in cooperative antigen transfer.
Article
Immunology
Yu Gao, Ruining Liu, Chenfei He, Juan Basile, Mattias Vesterlund, Marie Wahren-Herlenius, Alexander Espinoza, Cassandra Hokka-Zakrisson, Fahad Zadjali, Akihiko Yoshimura, Mikael Karlsson, Berit Carow, Martin E. Rottenberg
Summary: SOCS3 is a critical regulator of immune responses and inflammation, with its expression in thymic stromal cells being essential for T cell development and maintenance of thymus architecture. The inhibition of SOCS3 led to impaired thymocyte differentiation, proliferation, and increased apoptosis at different cell stages, ultimately affecting the generation of recent thymic emigrants in peripheral organs. The interaction between SOCS3 in thymic epithelial cells and TRIM 21 had significant implications for thymic cellularity and gene expression related to T cell selection and lympho-stromal interactions.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Immunology
Valentin P. Shichkin, Mariastefania Antica
Summary: The thymus is a complex organ consisting of different stromal cells and maturing T lymphocytes, and its function is mainly determined by the thymic stromal structure. Thymic epithelial cells and mesenchymal cells are the primary components of the thymus, playing a crucial role in T cell development and function. Understanding the signaling and transcriptional pathways underlying thymic cell interaction is essential for T cell differentiation and restoring thymic function after damage.
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
Medicine, Research & Experimental
Dong Zhang, Miaomiao Jia, Chuan Wang, Yingmin Li, Chunling Ma, Guiyun Zhu, Rufei Ma, Di Wen, Xianxian Jia, Guangming Xu, Xiaojing Zhang, Bin Cong
Summary: Immune balance is crucial for survival and is regulated by the nervous system. Evidence shows that cholecystokinin (CCK) and its receptors (CCKRs) play an important role in mediating immune response. However, the deficiency of CCKRs may impair immune balance. This study demonstrates that CCK2R is vital for CD4(+) T cell development in the thymus and plays a significant role in maintaining immune balance.
EXPERIMENTAL BIOLOGY AND MEDICINE
(2023)
Article
Biology
Bergithe E. Oftedal, Stefano Maio, Adam E. Handel, Madeleine P. J. White, Duncan Howie, Simon Davis, Nicolas Prevot, Ioanna A. Rota, Mary E. Deadman, Benedikt M. Kessler, Roman Fischer, Nikolaus S. Trede, Erdinc Sezgin, Rick M. Maizels, Georg A. Hollander
Summary: This study shows that the absence of the chaperonin subunit CCT8 in T cells severely impairs T cell activation, differentiation, and immune function. The deficiency in CCT-controlled protein folding leads to abnormal cellular stress response and inefficient immune protection against pathogens such as helminths.
COMMUNICATIONS BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Kathrin Jansen, Noriko Shikama-Dorn, Moustafa Attar, Stefano Maio, Maria Lopopolo, David Buck, Georg A. Hollander, Stephen N. Sansom
Summary: Thymic epithelial cells (TEC) play a crucial role in controlling the selection of T cells reactive to pathogens. A study found that mature mTEC express a higher percentage of protein-coding transcripts compared to peripheral tissues, but produce fewer isoforms for genes with tissue-restricted expression. Furthermore, it was discovered that TEC utilize a small number of peripheral splicing factors, including members of the RBFOX family, to generate a broad but selective representation of the peripheral splice isoform repertoire.
Article
Biochemistry & Molecular Biology
Lisa Schlicher, Paulina Kulig, Audrey von Munchow, Mark J. Murphy, Marcel P. Keller
Summary: Cenerimod, a potent S1P(1) receptor modulator, effectively prevents T and B cell migration in a concentration-dependent manner. This study provides insights into the molecular role of S1P(1) receptor and the potential therapeutic application of Cenerimod in autoimmune disorders.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Heather E. Stefanski, Yan Xing, Jemma Nicholls, Leslie Jonart, Emily Goren, Patricia A. Taylor, Alea A. Mills, Megan Riddle, John McGrath, Jakub Tolar, Georg A. Hollander, Bruce R. Blazar
Summary: Progressive immune deficiency of aging is characterized by severe thymic atrophy and contracted T cell repertoire. p63 plays a critical role in thymic development and maintenance, as well as hair follicle formation.
Article
Immunology
Thomas Fehr, Kerstin Huebel, Olivier de Rougemont, Irene Abela, Ariana Gaspert, Tayfun Guengoer, Mathias Hauri, Birgit Helmchen, Claudia Linsenmeier, Thomas Mueller, Jakob Nilsson, Oliver Riesterer, John D. Scandling, Urs Schanz, Pietro E. Cippa
Summary: This study reports the first European clinical trial on kidney transplantation aiming to induce immunological tolerance through mixed lymphohematopoietic chimerism. The results demonstrate that combined kidney and hematopoietic stem cell transplantation from an HLA-matched sibling is a feasible and successful approach, while maintaining immune responsiveness to mRNA vaccines.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Bettina E. Bernard, Emmanuelle Landmann, Lukas T. Jeker, Kathrin Schumann
Summary: Engineering human T cells for cancer, viral infections, and autoimmune diseases has been a dream for many immunologists and hematologists. The discovery and adaptation of CRISPR/Cas9 to human T cells have revolutionized the field, making T cell engineering more accessible and accelerating the development of engineered adoptive T cell therapies.
IMMUNOLOGY LETTERS
(2022)
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
Adam E. Handel, Stanley Cheuk, Fatima Dhalla, Stefano Maio, Tania Huebscher, Ioanna Rota, Mary E. Deadman, Olov Ekwall, Matthias Lutolf, Kenneth Weinberg, Georg Hollaender
Summary: This study explores the complex composition and dynamic changes of the non-epithelial stromal compartment in the thymus, and reveals the heterogeneity of different stromal subtypes and their roles in thymus organogenesis and tissue maintenance.
Article
Multidisciplinary Sciences
Marianne Dolz, Marko Hasiuk, John D. Gagnon, Mara Kornete, Romina Marone, Glenn Bantug, Robin Kageyama, Christoph Hess, K. Mark Ansel, Denis Seyres, Julien Roux, Lukas T. Jeker
Summary: CD28 provides the prototypical costimulatory signal for T cell activation. miR-17 similar to 92, induced by T cell receptor stimulation and enhanced by CD28 costimulation, acts as a central mediator for T cell activation by dampening negative regulators.
Article
Multidisciplinary Sciences
Marcel P. Trefny, Nicole Kirchhammer, Priska Auf der Maur, Marina Natoli, Dominic Schmid, Markus Germann, Laura Fernandez Rodriguez, Petra Herzig, Jonas Lotscher, Maryam Akrami, Jane C. Stinchcombe, Michal A. Stanczak, Andreas Zingg, Melanie Buchi, Julien Roux, Romina Marone, Leyla Don, Didier Lardinois, Mark Wiese, Lukas T. Jeker, Mohamed Bentires-Alj, Jeremie Rossy, Daniela S. Thommen, Gillian M. Griffiths, Heinz Laubli, Christoph Hess, Alfred Zippelius
Summary: In this study, a human antigen-specific ex vivo model was used to explore new therapeutic options for T cell immunotherapies. The protein SNX9 was identified as a mediator of T cell exhaustion, and its knockout resulted in enhanced memory differentiation and function of adoptively transferred T cells, improving anti-tumor efficacy of chimeric antigen receptor T cells in vivo.
NATURE COMMUNICATIONS
(2023)
Letter
Biophysics
Katharina Baur, Andreas Buser, Lukas T. Jeker, Nina Khanna, Heinz Laeubli, Dominik Heim, Jan C. Dirks, Corinne C. Widmer, Thomas Volken, Jakob R. Passweg, Andreas Holbro
BONE MARROW TRANSPLANTATION
(2023)
Article
Chemistry, Medicinal
Emmanuel A. Meyer, Paivi Aanismaa, Eric A. Ertel, Eva Huhn, Daniel S. Strasser, Markus Rey, Mark J. Murphy, Marianne M. Martinic, Laetitia Pouzol, Sylvie Froidevaux, Marcel P. Keller, Eva Caroff
Summary: The CXCR3 chemokine receptor plays a crucial role in immune response and inflammatory processes. In this study, a novel clinical compound called ACT-777991 was discovered as a potent and selective CXCR3 antagonist. It showed dose-dependent efficacy and target engagement in a mouse model of acute lung inflammation, indicating its potential therapeutic value.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Immunology
Marko Hasiuk, Marianne Dolz, Romina Marone, Lukas T. Jeker
Summary: Cellular therapy has evolved from traditional blood transfusion to complex manufacturing of CAR-T cells. Basic knowledge of cell biology and molecular genetics can improve modern cellular therapy products. Although most cell engineering efforts focus on proteins, miRNAs also play an important role in posttranscriptional gene regulation.
IMMUNOLOGY LETTERS
(2023)
Article
Immunology
Romina Marone, Emmanuelle Landmann, Anna Devaux, Rosalba Lepore, Denis Seyres, Jessica Zuin, Thomas Burgold, Corinne Engdahl, Giuseppina Capoferri, Alessandro Dell'Aglio, Clement Larrue, Federico Simonetta, Julia Rositzka, Manuel Rhiel, Geoffroy Andrieux, Danielle N. Gallagher, Markus S. Schroder, Amelie Wiederkehr, Alessandro Sinopoli, Valentin Do Sacramento, Anna Haydn, Laura Garcia-Prat, Christopher Divsalar, Anna Camus, Liwen Xu, Lorenza Bordoli, Torsten Schwede, Matthew Porteus, Jerome Tamburini, Jacob E. Corn, Toni Cathomen, Tatjana I. Cornu, Stefanie Urlinger, Lukas T. Jeker
Summary: Targeted immunotherapy against CD123 shows promise for hematologic diseases, but the shared expression on healthy hematopoietic stem cells poses risks. Epitope-engineered HSPCs can be shielded from immunotherapy while remaining functional. Transplantation of genome-edited HSPCs enables tumor-selective immunotherapy and reconstruction of a fully functional hematopoietic system.
JOURNAL OF EXPERIMENTAL MEDICINE
(2023)
Article
Cell Biology
Fernando P. Canale, Julia Neumann, Janusz von Renesse, Elisabetta Loggi, Matteo Pecoraro, Ian Vogel, Giada Zoppi, Gaia Antonini, Tobias Wolf, Wenjie Jin, Xiaoqin Zheng, Giuliano La Barba, Emrullah Birgin, Marianne Forkel, Tobias Nilsson, Romina Marone, Henrik Mueller, Nadege Pelletier, Lukas T. Jeker, Gianluca Civenni, Christoph Schlapbach, Carlo V. Catapano, Lena Seifert, Adrian M. Seifert, Silke Gillessen, Sara De Dosso, Alessandra Cristaudi, Nuh N. Rahbari, Giorgio Ercolani, Roger Geiger
Summary: Understanding how immune cells become dysfunctional in tumors is crucial for developing advanced immunotherapies. Our study revealed that certain proteins, such as SGPL1 and AFAP1L2, play a role in dampening the inflammatory response and anti-tumor function of macrophages and CD8+ T cells in liver cancer. Targeting these proteins could enhance the effectiveness of immunotherapy.
