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
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
Cell Biology
Jiali Yang, Juan Liu, Jiayu Liang, Fan Li, Wenwen Wang, Huan Chen, Xiang Xie
Summary: The thymus is a critical immune organ that plays important roles in the body's physiological and pathological processes. However, it undergoes degenerative changes with aging, leading to decreased immune function and increased risk of age-associated diseases. This review explores the role of epithelial-mesenchymal transition (EMT) in thymic involution and summarizes current interventions for reversing this process. Understanding the mechanisms of thymic involution through EMT may lead to the development of new therapies for age-associated diseases.
AGEING RESEARCH REVIEWS
(2023)
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
Biochemistry & Molecular Biology
Marion Gransagne, Gabriel Ayme, Sebastien Brier, Gaelle Chauveau-Le Friec, Veronique Meriaux, Mireille Nowakowski, Francois Dejardin, Sylvain Levallois, Guilherme Dias de Melo, Flora Donati, Matthieu Prot, Sebastien Brule, Bertrand Raynal, Jacques Bellalou, Pedro Goncalves, Xavier Montagutelli, James P. Di Santo, Francoise Lazarini, Patrick England, Stephane Petres, Nicolas Escriou, Pierre Lafaye
Summary: This study developed a sandwich immunoassay to specifically detect the nucleoprotein (N) of SARS-CoV-2. Seven antibodies were identified that recognized the full N protein and did not cross react with nucleoproteins from common human coronaviruses. The antibodies mainly targeted conformational epitopes in the C-terminal or N-terminal domains and were able to detect SARS-CoV-2 variants.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Immunology
Elza Evren, Emma Ringqvist, Jean-Marc Doisne, Anna Thaller, Natalie Sleiers, Richard A. Flavell, James P. Di Santo, Tim Willinger
Summary: Evren et al. identify CD116(+) fetal liver cells as precursors of human alveolar macrophages in early life and reveal the impact of cell origin on lung macrophage identity and function.
JOURNAL OF EXPERIMENTAL MEDICINE
(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.
Article
Developmental Biology
Pedro Ferreirinha, Ruben G. R. Pinheiro, Jonathan J. M. Landry, Nuno L. Alves
Summary: This study identified two distinct subsets of thymic fibroblasts, CD140 alpha beta(+)GP38(+)SCA-1(-) and CD140 alpha beta(+)GP38(+)SCA-1(+), with different developmental features. CD140 alpha beta(+)GP38(+)SCA-1(-) was identified as a source of fibroblast progenitors, while CD140 alpha beta(+)GP38(+)SCA-1(+) represented a mature subset. Furthermore, the study found that thymic crosstalk is crucial for fibroblast maturation.
Article
Multidisciplinary Sciences
Nicolas Serafini, Angelique Jarade, Laura Surace, Pedro Goncalves, Odile Sismeiro, Hugo Varet, Rachel Legendre, Jean-Yves Coppee, Olivier Disson, Scott K. Durum, Gad Frankel, James P. Di Santo
Summary: Group 3 innate lymphoid cells (ILC3s) in the intestine remain activated for months after exposure to Citrobacter rodentium, leading to enhanced immune response and defense capability. These trained ILC3s undergo metabolic changes and exhibit enhanced proliferative capacity and IL-22 production.
Article
Oncology
Saketh S. Dinavahi, Yu-Chi Chen, Kishore Punnath, Arthur Berg, Meenhard Herlyn, Momeneh Foroutan, Nicholas D. Huntington, Gavin P. Robertson
Summary: The targeting of the AKT/WEE1 pathways to induce p53 activation is a novel and effective approach to inhibit tumor development. This study shows that this approach can enhance tumor immunogenicity, induce immunogenic cell death, and recruit immune cells in the tumor microenvironment, resulting in tumor regression.
CANCER IMMUNOLOGY RESEARCH
(2022)
Article
Oncology
Pierre-Louis Bernard, Rebecca Delconte, Sonia Pastor, Vladimir Laletin, Cathy Costa Da Silva, Armelle Goubard, Emmanuelle Josselin, Remy Castellano, Adrien Krug, Julien Vernerey, Raynier Devillier, Daniel Olive, Els Verhoeyen, Eric Vivier, Nicholas D. Huntington, Jacques Nunes, Geoffrey Guittard
Summary: This study investigates the impact of targeting an inhibiting protein called CISH in natural killer (NK) cells on their functions and antitumor properties. The results show that CISH deletion enhances NK cell activation and killing abilities, while limiting NK cell exhaustion. Furthermore, CISH deletion optimizes NK cell accumulation in tumors and improves the effectiveness of antitumor responses. Therefore, CISH has been validated as a potential therapeutic target to enhance NK cell immunotherapy.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Review
Hematology
Laura Surace, James P. Di Santo
Summary: This review discusses the role of innate lymphoid cells (ILCs) as metabolic sentinels and how specific activities of ILC subsets influence homeostasis and disease. Recent studies have found that ILCs' metabolism, phenotype, and function are shaped by signals from the tissue microenvironment. ILCs have emerged as crucial sensors of metabolic stress.
CURRENT OPINION IN HEMATOLOGY
(2022)
Article
Multidisciplinary Sciences
Ashleigh R. Poh, Christopher G. Love, David Chisanga, James H. Steer, David Baloyan, Michael Chopin, Stephen Nutt, Jai Rautela, Nicholas D. Huntington, Nima Etemadi, Megan O'Brien, Ryan O'Keefe, Lesley G. Ellies, Christophe Macri, Justine D. Mintern, Lachlan Whitehead, Gangadhara Gangadhara, Louis Boon, Ashwini L. Chand, Clifford A. Lowell, Wei Shi, Fiona J. Pixley, Matthias Ernst
Summary: Genetic ablation or therapeutic inhibition of the myeloid-specific hematopoietic cell kinase (HCK) enhances the response to immunotherapy by modifying the tumor microenvironment and promoting immune cell activation.
Review
Immunology
Laura G. G. Sousa, Pedro M. M. Rodrigues, Nuno L. L. Alves
Summary: Within the thymus, thymic epithelial cells play a crucial role in the selection of functional T cells expressing a diverse and self-tolerant T-cell receptor repertoire. This review summarizes recent studies on the composition of cortical and medullary TEC microenvironments and discusses the molecular processes controlling TEC function in T-cell selection, particularly the role of cortical TECs in positive selection and the generation of self-peptides:MHC II complexes.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2023)
Article
Cell Biology
Lizeth G. Meza Guzman, Craig D. Hyland, Grace M. Bidgood, Evelyn Leong, Zihan Shen, Wilford Goh, Jai Rautela, James E. Vince, Sandra E. Nicholson, Nicholas D. Huntington
Summary: The clinical development of NK cell-mediated immunotherapy is a significant milestone in cancer treatment, but improving NK cell persistence and overcoming tumor microenvironment suppression are challenges. This study explores the role of CD45 in NK cell homeostasis and shows that CD45 deficiency does not enhance NK cell persistence, but instead results in a developmental defect. Inhibiting CD45 in progenitor or stem cell populations may improve the yield of in vitro generated NK cells for adoptive therapy.
IMMUNOLOGY AND CELL BIOLOGY
(2023)
Article
Immunology
Nicholas D. Huntington
Summary: IRF4 is necessary for the differentiation of T cells, B cells, and some myeloid cells. A recent study reveals that IRF4 is upregulated after natural killer (NK) cell activation and is essential for the differentiation and expansion of virus-specific NK cells by regulating nutrient acquisition, including iron uptake.
Article
Multidisciplinary Sciences
Shuwei Liang, Eric Tran, Xin Du, Jiajun Dong, Harrison Sudholz, Hao Chen, Zihan Qu, Nicholas D. Huntington, Jeffrey J. Babon, Nadia J. Kershaw, Zhong-Yin Zhang, Jonathan B. Baell, Florian Wiede, Tony Tiganis
Summary: In this study, the authors demonstrate that inhibition of PTP1B and PTPN2 in tumor cells and T cells with a small molecule inhibitor represses the growth of immunogenic and cold tumors, and enhances response to anti-PD-1 immunotherapy without promoting immune-related toxicities.
NATURE COMMUNICATIONS
(2023)
Article
Immunology
Shengbo Zhang, Jai Rautela, Naiara G. Bediaga, Tatiana B. Kolesnik, Yue You, Junli Nie, Laura F. Dagley, Justin Bedo, Hanqing Wang, Li Sun, Robyn Sutherland, Elliot Surgenor, Nadia Iannarella, Rhys Allan, Fernando Souza-Fonseca-Guimaraes, Yi Xie, Qike Wang, Yuxia Zhang, Yuekang Xu, Stephen L. Nutt, Andrew M. Lew, Nicholas D. Huntington, Sandra E. Nicholson, Michael Chopin, Yifan Zhan
Summary: The cytokine GM-CSF can differentiate monocytes into macrophages with opposing functions, proinflammatory M1-like and immunosuppressive M2-like. In this study, it was found that the protein CIS plays a critical role in the GM-CSF signaling pathway, and deficiency of CIS leads to the differentiation of monocytes into immunosuppressive M2-like macrophages, promoting allergic inflammation.
CELLULAR & MOLECULAR IMMUNOLOGY
(2023)
Article
Oncology
Fernando Souza-Fonseca-Guimaraes, Gustavo R. Rossi, Laura F. Dagley, Momeneh Foroutan, Timothy R. McCulloch, Jumana Yousef, Hae-Young Park, Jennifer H. Gunter, Paul A. Beavis, Cheng-Yu Lin, Soroor Hediyeh-Zadeh, Tania Camilleri, Melissa J. Davis, Nicholas D. Huntington
CANCER IMMUNOLOGY RESEARCH
(2022)