Biomaterial Database

Transcriptional factor ATF3 protects against colitis by regulating follicular helper T cells in Peyer's patches. 2019

Yingjiao Cao, and Qiong Yang, and Hui Deng, and Jinyi Tang, and Jiancong Hu, and Huanliang Liu, and Min Zhi, and Linsen Ye, and Bin Zou, and Yongdong Liu, and Lai Wei, and Dmitry I Gabrilovich, and Haikun Wang, and Jie Zhou

Joint Program in Immunology, Department of Internal Medicine, Affiliated Guangzhou Women and Children's Medical Center, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510623, China.

Disruption of mucosal immunity plays a critical role in the pathogenesis of inflammatory bowel disease, yet its mechanism remains not fully elucidated. Here, we found that activating transcription factor 3 (ATF3) protects against colitis by regulating follicular helper T (TFH) cells in the gut. The expression of ATF3 in CD4+ T cells was negatively correlated with the severity of ulcerative colitis in clinical patients. Mice with ATF3 deficiency in CD4+ T cells (CD4Atf3 ) were much more susceptible to dextran sulfate sodium-induced colitis. The frequencies of TFH cells, not other T cell subsets, were dramatically decreased in Peyer's patches from CD4Atf3 mice compared with Atf3 littermate controls. The defective TFH cells significantly diminished germinal center formation and IgA production in the gut. Importantly, adoptive transfer of TFH or IgA+ B cells caused significant remission of colitis in CD4Atf3 mice, indicating the TFH-IgA axis mediated the effect of ATF3 on gut homeostasis. Mechanistically, B cell lymphoma 6 was identified as a direct transcriptional target of ATF3 in CD4+ T cells. In summary, we demonstrated ATF3 as a regulator of TFH cells in the gut, which may represent a potential immunotherapeutic target in colitis.

UI	MeSH Term	Description	Entries
D007070	Immunoglobulin A	Represents 15-20% of the human serum immunoglobulins, mostly as the 4-chain polymer in humans or dimer in other mammals. Secretory IgA (IMMUNOGLOBULIN A, SECRETORY) is the main immunoglobulin in secretions.	IgA,IgA Antibody,IgA1,IgA2,Antibody, IgA
D007167	Immunotherapy	Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection.	Immunotherapies
D010581	Peyer's Patches	Lymphoid tissue on the mucosa of the small intestine.	Patches, Peyer's,Peyer Patches,Peyers Patches
D003092	Colitis	Inflammation of the COLON section of the large intestine (INTESTINE, LARGE), usually with symptoms such as DIARRHEA (often with blood and mucus), ABDOMINAL PAIN, and FEVER.	Colitides
D003093	Colitis, Ulcerative	Inflammation of the COLON that is predominantly confined to the MUCOSA. Its major symptoms include DIARRHEA, rectal BLEEDING, the passage of MUCUS, and ABDOMINAL PAIN.	Colitis Gravis,Idiopathic Proctocolitis,Inflammatory Bowel Disease, Ulcerative Colitis Type,Ulcerative Colitis
D003106	Colon	The segment of LARGE INTESTINE between the CECUM and the RECTUM. It includes the ASCENDING COLON; the TRANSVERSE COLON; the DESCENDING COLON; and the SIGMOID COLON.	Appendix Epiploica,Taenia Coli,Omental Appendices,Omental Appendix,Appendices, Omental,Appendix, Omental
D004195	Disease Models, Animal	Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases.	Animal Disease Model,Animal Disease Models,Disease Model, Animal
D006377	T-Lymphocytes, Helper-Inducer	Subpopulation of CD4+ lymphocytes that cooperate with other lymphocytes (either T or B) to initiate a variety of immune functions. For example, helper-inducer T-cells cooperate with B-cells to produce antibodies to thymus-dependent antigens and with other subpopulations of T-cells to initiate a variety of cell-mediated immune functions.	Helper Cell,Helper Cells,Helper T Cell,Helper-Inducer T-Lymphocytes,Inducer Cell,Inducer Cells,T-Cells, Helper-Inducer,T-Lymphocytes, Helper,T-Lymphocytes, Inducer,Helper T-Cells,Cell, Helper T,Cells, Helper T,Helper Inducer T Lymphocytes,Helper T Cells,Helper T-Cell,Helper T-Lymphocyte,Helper T-Lymphocytes,Helper-Inducer T-Cell,Helper-Inducer T-Cells,Helper-Inducer T-Lymphocyte,Inducer T-Lymphocyte,Inducer T-Lymphocytes,T Cell, Helper,T Cells, Helper,T Cells, Helper Inducer,T Lymphocytes, Helper,T Lymphocytes, Helper Inducer,T Lymphocytes, Inducer,T-Cell, Helper,T-Cell, Helper-Inducer,T-Cells, Helper,T-Lymphocyte, Helper,T-Lymphocyte, Helper-Inducer,T-Lymphocyte, Inducer
D006706	Homeostasis	The processes whereby the internal environment of an organism tends to remain balanced and stable.	Autoregulation
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia