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

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 − FoxP3 high TFR cells were decreased while CD226 + and CD45RA + FoxP3 int 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.

Ustekinumab Inhibits T Follicular Helper Cell Differentiation in Patients With Crohn’s Disease

“…TFH cells may be defined as CXCR5+ CD4+ cells yielding TFH cell frequencies around 20% in peripheral blood ( Figure 1 C ). 33 TFH cell frequencies are considerably lower if more specific markers such as PD-1 or ICOS are used (2%–10%) 26 and are well in the range of the frequencies we describe here when CXCR5+ PD-1 high cells are analyzed. 34 Importantly, this subset most closely resembles lymphatic tissue–derived TFH cells.…”

Activated inducible co-stimulator-positive programmed cell death 1-positive follicular helper T cells indicate disease activity and severity in ulcerative colitis patients

“…We previously reported that active UC patients possessed higher levels of Tfh cells and CXCR3 − CCR6 − Tfh2 subsets but decreased Tfr cells in peripheral blood [9]. In order to further our research, we studied the expression of ICOS and PD-1 on Tfh cells.…”

“…Tfh cells are crucial for the differentiation and development of B cells, and abnormality of effective B cells was confirmed to be involved in the pathogenesis of UC [9][10][11][12][13]. To further study the clinical significance of circulating ICOS + , PD-1 + and ICOS + PD-1 + Tfh cells in the pathogenesis of UC, we analyzed their associations with functional B cell subsets.…”

“…In contrast, Tfr cells have an inhibitory effect on Tfh and germinal center B cells [12,14]. An imbalance of Tfr and Tfh cells may induce diseases mediated by abnormal B cell immunity [9,15,16]. Xue et al reported that Tfh cells and interleukin (IL)-21 were significantly higher in UC patients than in healthy controls [17].…”

“…Several kinds of autoantibodies secreted by functional B cells have been found to participate in the onset and exacerbation of UC [3,4,7,8]. Our previous research found that CD19 + CD24 − CD38 − new memory B cells and CD19 + CD24 − CD38 high plasmablasts cells in active UC were significantly increased and were positively correlated with disease severity [9].…”