The Imbalance of Circulating Follicular Helper T Cells and Follicular Regulatory T Cells Is Associated With Disease Activity in Patients With Ulcerative Colitis

Yan Long,Chunhong Fan,Xiaotao Zhao,Changsheng Xia,Chen Liu,Huizhang Bao,Lijuan Xu,Caoyi Liu

doi:10.3389/fimmu.2020.00104

Yan Long, Chunhong Fan + Show 6 more

Open Access

https://doi.org/10.3389/fimmu.2020.00104

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Abstract

Ulcerative colitis (UC) is a chronic inflammatory bowel disease affecting the colon and rectum, in which the abnormality of B cells is involved in both its pathogenesis and progression. Follicular helper T cells (TFH) play an important role in assisting the immune function of human B cells in germinal centers, and follicular regulatory T cells (TFR) have the function of inhibiting TFH and germinal center B cell responses. The significance of circulating TFH and TFR in ulcerative colitis (UC) remains unclear. We analyzed peripheral blood of active and stable remission UC patients and found that circulating TFR was significantly decreased while TFH was increased in active UC patients. As to TFH subsets, TFH2 was elevated while TFH17 was decreased in active UC, with IL-4/IL-17A secretion enhanced. Helios+ and CD45RA−FoxP3high TFR cells were decreased while CD226+ and CD45RA+FoxP3int TFR cells were increased in active UC patients. The levels of new memory B cells, plasmablasts and serum IgG were significantly increased in active UC patients, and were positively correlated with TFH and TFH2, and negatively correlated with TFR. Serum CRP and Mayo Clinic scores were positively correlated with TFH and TFH2 but negatively correlated with TFR. Serum IL-12 and IL-21 were up-regulated while IL-10 was down-regulated in active UC. To conclude, an imbalance of circulating TFH and TFR cells is associated with disease activity in UC patients. Our results suggest a new mechanism for TFH and TFR imbalance in the pathogenesis of UC, providing a new perspective for theoretical research and therapeutic strategies for UC.

Highlights

Ulcerative colitis (UC) is a chronic inflammatory bowel disease affecting the colon and rectum and the recurrence of UC appears as alternative between active and remission periods, which has the risk of developing into colitis-related cancer [1, 2]
We calculated the ratio of follicular regulatory T cells (TFR)/follicular helper T cells (TFH), and found it was significantly lower in active UC patients, compared with healthy controls (HC) and stable remission UC patients (Figure 1C)
We found that peripheral TFR cells were significantly decreased and functional TFR subsets were decreased in active UC, while TFH cells were significantly elevated and the composition of TFH were altered with a predominant increase of TFH2 and a significant decrease of TFH17

Summary

Introduction

Ulcerative colitis (UC) is a chronic inflammatory bowel disease affecting the colon and rectum and the recurrence of UC appears as alternative between active and remission periods, which has the risk of developing into colitis-related cancer [1, 2]. During the active period of UC, the mucosal pathology is expressed as massive neutrophils, lymphocytes and plasma cell infiltration, and lymphoid follicle formation in gut-associated lymphoid tissues (GALT) [3]. An abnormal number and function of B cells caused by the interaction between T and B cells are involved in the pathogenesis of UC [4,5,6,7,8]. There are a large number of activated B cells in the lamina propria of UC patients, and a large amount of IgG is expressed in the lesion tissues [6].

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