The Role of T Follicular Helper Cells and Interleukin-21 in the Pathogenesis of Inflammatory Bowel Disease

Abstract

T follicular helper (Tfh) cells represent a novel subset of CD4+ T cells which can provide critical help for germinal center (GC) formation and antibody production. The Tfh cells are characterized by the expression of CXC chemokine receptor 5 (CXCR5), programmed death 1 (PD-1), inducible costimulatory molecule (ICOS), B cell lymphoma 6 (BCL-6), and the secretion of interleukin-21 (IL-21). Given the important role of Tfh cells in B cell activation and high-affinity antibody production, Tfh cells are involved in the pathogenesis of many human diseases. Inflammatory bowel disease (IBD) is a group of chronic inflammatory diseases characterized by symptoms such as diarrhea, abdominal pain, and weight loss. Ulcerative colitis (UC) and Crohn’s disease (CD) are the most studied types of IBD. Dysregulated mucosal immune response plays an important role in the pathogenesis of IBD. In recent years, many studies have identified the critical role of Tfh cells and IL-21 in the pathogenic process IBD. In this paper, we will discuss the role of Tfh cells and IL-21 in IBD pathogenesis.

Follicular helper T lymphocytes in the endometria of patients with reproductive failure: Association with pregnancy outcomes and inflammatory status of the endometria

“…45 Since then, clinical and laboratory findings have consistently revealed abnormal Tfh cell responses in patients with autoimmune and inflammatory diseases. 46,47 Tfh cell number and activation status have been reported to be associated with disease activity, autoantibody levels, and response to conventional therapy. 48 However, unlike mouse studies where lymphatic organs are readily available in disease conditions, studies on human autoimmune disorders have mainly focused on circulating Tfh cells.…”

“…Early observations in mouse models, notably in lupus predisposition, demonstrated the pathogenic role of hyperactivated Tfh cell responses in autoimmunity 45 . Since then, clinical and laboratory findings have consistently revealed abnormal Tfh cell responses in patients with autoimmune and inflammatory diseases 46,47 . Tfh cell number and activation status have been reported to be associated with disease activity, autoantibody levels, and response to conventional therapy 48 .…”

CXCL13 is elevated in inflammatory bowel disease in mice and humans and is implicated in disease pathogenesis

“…In our study, the selected patients were all newly diagnosed IBD patients at the early stage of the disease. In addition, CD4+CXCR5+ T cells included not only CD4+CXCR5+Foxp3- T follicular helper (Tfh) cells, but also CD4+CXCR5+Foxp3+ T follicular regulator (Tfr) cells ( 24 , 25 ). Furthermore, Cxcl13 -/- knockout mice were used to construct DSS-induced colitis model to verify the role of CXCL13 in IBD.…”