Article
Biology
Soeun Kim, Guk-Yeol Park, Jong Seok Park, Jiho Park, Hyebeen Hong, Yoontae Lee
Summary: The transcriptional repressor Capicua (CIC) plays a critical role in controlling thymic selection process, impacting both positive and negative selection of thymocytes. CIC deficiency attenuates TCR signaling in DP cells and regulates multiple genes involved in T cell development, suggesting it serves as a safeguard against autoimmunity.
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)
Review
Immunology
Magali Irla
Summary: During thymic development, signals provided by specific cells control the selection of T cells, resulting in the generation of a T cell repertoire capable of responding to foreign antigens while tolerating self-antigens. This review summarizes our current understanding of the signals involved in the selection of regulatory T cells and highlights the functional diversity of thymic antigen-presenting cell subsets implicated in T cell selection.
ANNUAL REVIEW OF IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Reema Jain, Kelin Zhao, Julie M. Sheridan, Melanie Heinlein, Fiona Kupresanin, Waruni Abeysekera, Cathrine Hall, James Rickard, Philippe Bouillet, Henning Walczak, Andreas Strasser, John Silke, Daniel H. D. Gray
Summary: The study reveals the crucial role of the linear ubiquitin chain assembly complex in thymic epithelial cell differentiation and survival, with deficiency in LUBAC proteins severely impacting thymic tissue expansion and cell survival, potentially leading to premature thymic atrophy.
CELL DEATH AND DIFFERENTIATION
(2021)
Article
Biochemistry & Molecular Biology
Ling Wang, Lingyang Jing, Qingyu Zhang, Shoude Li, Yi Wang, Hongfeng Zhao
Summary: The human-induced lead contamination has serious environmental consequences and poses severe risks to wildlife. This study investigated the toxic effects of lead on avian thymus using Japanese quails as a biological model. The results showed that lead exposure caused morphological, structural, and molecular signaling damage to the avian thymus, leading to immunosuppression.
JOURNAL OF INORGANIC BIOCHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Marte Heimli, Siri Tennebo Flam, Hanne Sagsveen Hjorthaug, Pal Marius Bjornstad, Maria Chernigovskaya, Quy Khang Le, Xavier Tekpli, Victor Greiff, Benedicte Alexandra Lie
Summary: The study indicates that the adaptive immune receptor repertoire may influence the differentiation of thymocytes, providing insights for the development of therapies for immune-mediated diseases.
SCIENTIFIC REPORTS
(2023)
Article
Biochemistry & Molecular Biology
Matthias Kaestle, Camilla Merten, Roland Hartig, Carlos Plaza-Sirvent, Ingo Schmitz, Ursula Bommhardt, Burkhart Schraven, Luca Simeoni
Summary: Lck plays a crucial role in TCR signaling and has been found to have a novel function downstream, regulating thymocyte differentiation and selection.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Daniel F. Zegarra-Ruiz, Dasom V. Kim, Kendra Norwood, Myunghoo Kim, Wan-Jung H. Wu, Fatima B. Saldana-Morales, Andrea A. Hill, Shubhabrata Majumdar, Stephanie Orozco, Rickesha Bell, June L. Round, Randy S. Longman, Takeshi Egawa, Matthew L. Bettini, Gretchen E. Diehl
Summary: Humans and their microbiota have a mutually beneficial relationship, where microbiota provides nutritional benefits and protection, and humans provide a hospitable environment. Maintaining this relationship requires immune balance to contain commensal microorganisms and limit inflammatory responses. Intestinal microorganisms can be recognized by T cells with antigen-specificity.
Article
Multidisciplinary Sciences
Shintaro Funasaki, Atsushi Hatano, Hirokazu Nakatsumi, Daisuke Koga, Osamu Sugahara, Kanae Yumimoto, Masaya Baba, Masaki Matsumoto, Keiichi I. Nakayama
Summary: CD4(+)CD8(+) double-positive (DP) thymocytes undergo positive or negative selection based on the strength of TCR stimulation. Phosphoproteome analysis revealed that high-affinity peptide ligands induce phosphorylation of p90 ribosomal protein kinase (RSK) at Thr562. This phosphorylation triggers RSK translocation to the nucleus, where it phosphorylates the nuclear receptor Nur77, promoting its mitochondrial translocation for apoptosis induction.
Article
Multidisciplinary Sciences
Lei Xu, Chuan Wei, Ying Chen, Yue Wu, Xiaoli Shou, Wenjie Chen, Di Lu, Haoran Sun, Wei Li, Beibei Yu, Xiaowei Wang, Xiaojun Zhang, Yanxiong Yu, Zhigang Lei, Rui Tang, Jifeng Zhu, Yalin Li, Linrong Lu, Hong Zhou, Sha Zhou, Chuan Su, Xiaojun Chen
Summary: Severe infection commonly leads to immunosuppression, impairing pathogen clearance and increasing susceptibility to secondary infection. This study uncovers the role of IL-33 in immunosuppression by inducing thymic involution-associated naive T cell dysfunction and disrupting T cell aging. The findings suggest that targeting IL-33 or ST2 may be a promising strategy to rejuvenate T cell immunity and better control severe infection.
NATURE COMMUNICATIONS
(2022)
Article
Immunology
Tianzhuo Zhang, Qianwen Shi, Huining Gu, Biaoyi Yu, Sha Yin, Qing Ge, Xiaoning Mo, Xiaofeng Liu, Jing Huang
Summary: CCDC134 is a cytokine-like molecule that serves as a positive regulator of TCR-proximal signaling by interacting with CD3e and modulating its ubiquitination and degradation. T cell-specific deletion of Ccdc134 results in decreased mature CD4(+) and CD8(+) T cells, impaired T cell homeostasis, and attenuated response to TCR stimulation in vitro and in vivo. These findings highlight the importance of CCDC134 in T cell development and function, and its role in T cell-mediated inflammatory and antitumor responses.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Phillip P. Domeier, Ziaur S. M. Rahman, Steven F. Ziegler
Summary: Long-lived and high-affinity antibodies are regulated by the cytokine thymic stromal lymphopoietin (TSLP), which affects the formation of germinal centers (GC) and antigen-specific antibody responses. TSLP signaling on T cells promotes the retention of antigen-specific B cells and TFH differentiation, while TSLP signaling on B cells regulates the generation of antigen-specific memory B cells. TSLP in both cell types promotes the expression of interferon regulatory factor 4 (IRF4), which is crucial for efficient GC activity.
SCIENCE IMMUNOLOGY
(2023)
Article
Cell Biology
Weihong Gu, Darling Melany C. Madrid, Sebastian Joyce, John P. Driver
Summary: In this study, single-cell RNA sequencing was used to create a cell atlas of the early-adolescent pig thymus, revealing conserved features and species-specific differences compared to human thymocytes. The study also identified unconventional T cell types with gene expression profiles associated with innate effector functions and characterized the functional diversity of pig iNKT cells. These findings provide important insights into pig T cell development.
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
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)