Back to Search
Start Over
T follicular helper cells restricted by IRF8 contribute to T cell-mediated inflammation.
- Source :
-
Journal of Autoimmunity . Jan2019, Vol. 96, p113-122. 10p. - Publication Year :
- 2019
-
Abstract
- Abstract The follicular helper T cell (T FH) are established regulators of germinal center (GC) B cells, whether T FH have pathogenic potential independent of B cells is unknown. Based on in vitro T FH cell differentiation, in vivo T cell transfer animal colitis model, and intestinal tissues of inflammatory bowel disease (IBD) patients, T FH and its functions in colitis development were analyzed by FACS, ChIP, ChIP-sequencing, WB, ELISA and PCR. Herein we demonstrate that intestinal tissues of patients and colon tissues obtained from Rag1 −/− recipients of naïve CD4+ T cells with colitis, each over-express T FH -associated gene products. Adoptive transfer of naïve Bcl6 −/− CD4+ T cells into Rag1 −/− recipient mice abrogated development of colitis and limited T FH differentiation in vivo , demonstrating a mechanistic link. In contrast, T cell deficiency of interferon regulatory factor 8 (IRF8) resulted in augmentation of T FH induction in vitro and in vivo. Functional studies showed that adoptive transfer of IRF8 deficient CD4+ T cells into Rag1 −/− recipients exacerbated colitis development associated with increased gut T FH -related gene expression, while Irf8 −/− /Bcl6 −/− CD4+ T cells abrogated colitis, together indicating that IRF8-regulated T FH can directly cause colon inflammation. Molecular analyses revealed that IRF8 suppresses T FH differentiation by inhibiting transcription and transactivation of the TF IRF4, which is also known to be essential for T FH induction. Our documentation showed that IRF8-regulated T FH can function as B-cell-independent, pathogenic, mediators of colitis suggests that targeting T FH could be effective for treatment of IBD. Highlights • Our study reveals that T FH cells are critically involved in the development of T cell-mediated inflammatory diseases. • The study defines IRF8 as an important intrinsic suppressor of T FH differentiation. • Our studies are really novel and will lead to more exciting investigations concerning the contributions of T FH cells in the development of various T cell-mediated inflammatory diseases in future. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 08968411
- Volume :
- 96
- Database :
- Academic Search Index
- Journal :
- Journal of Autoimmunity
- Publication Type :
- Academic Journal
- Accession number :
- 133720817
- Full Text :
- https://doi.org/10.1016/j.jaut.2018.09.001