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

Journal of Autoimmunity
Ruihua ZhangHuabao Xiong

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-related gene expression, while Irf8-/-/Bcl6-/- CD4+ T cells abrogated colitis, together indicating that IRF8-regulated TFH can ...Continue Reading

Citations

Jun 26, 2020·Frontiers in Physiology·Xue-Ke LiuDuan-Yong Liu
Aug 9, 2020·Journal of Immunology Research·Long-Shan JiYue-Qiu Gao
Nov 7, 2019·Journal of Immunology Research·Li WangSong Qin
Nov 18, 2020·The Journal of Experimental Medicine·Achia KhatunWeiguo Cui
Sep 3, 2021·Gastroenterology Research and Practice·Lulu SunDashan Wang

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