T follicular helper cells restricted by IRF8 contribute to T cell-mediated inflammation.

T follicular helper cells restricted by IRF8 contribute to T cell-mediated inflammation.
J Autoimmun. 2018 Sep 18;:
Authors: Zhang R, Qi CF, Hu Y, Shan Y, Hsieh YP, Xu F, Lu G, Dai J, Gupta M, Cui M, Peng L, Yang J, Xue Q, Chen-Liang R, Chen K, Zhang Y, Fung-Leung WP, Mora JR, Li L, Morse HC, Ozato K, Heeger PS, Xiong H
Abstract
The follicular helper T cell (TFH) are established regulators of germinal center (GC) B cells, whether TFH have pathogenic potential independent of B cells is unknown. Based on in vitro TFH cell differentiation, in vivo T cell transfer animal colitis model, and intestinal tissues of inflammatory bowel disease (IBD) patients, TFH 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 TFH-associated gene products. Adoptive transfer of naïve Bcl6-/- CD4+ T cells into Rag1-/- recipient mice abrogated development of colitis and limited TFH differentiation in vivo, demonstrating a mechanistic link. In contrast, T cell deficiency of interferon regulatory factor 8 (IRF8) resulted in augmentation of TFH 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 TFH-rela...

Source: Journal of Autoimmunity - September 18, 2018 Category: Allergy & Immunology Authors: Zhang R, Qi CF, Hu Y, Shan Y, Hsieh YP, Xu F, Lu G, Dai J, Gupta M, Cui M, Peng L, Yang J, Xue Q, Chen-Liang R, Chen K, Zhang Y, Fung-Leung WP, Mora JR, Li L, Morse HC, Ozato K, Heeger PS, Xiong H Tags: J Autoimmun Source Type: research