| First Author | Cao Y | Year | 2019 |
| Journal | Proc Natl Acad Sci U S A | Volume | 116 |
| Issue | 13 | Pages | 6286-6291 |
| PubMed ID | 30862736 | Mgi Jnum | J:273871 |
| Mgi Id | MGI:6286174 | Doi | 10.1073/pnas.1818164116 |
| Citation | Cao Y, et al. (2019) Transcriptional factor ATF3 protects against colitis by regulating follicular helper T cells in Peyer's patches. Proc Natl Acad Sci U S A 116(13):6286-6291 |
| abstractText | 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 (CD4 (cre) Atf3 (fl/fl) ) 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 CD4 (cre) Atf3 (fl/fl) mice compared with Atf3 (fl/fl) 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 CD4 (cre) Atf3 (fl/fl) 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. |
