GITR Promotes the Polarization of TFH-Like Cells in Helicobacter pylori-Positive Gastritis

Abstract

Gastric CD4+T cells contribute to Helicobacter pylori (H. pylori)-induced gastritis by amplifying mucosal inflammation and exacerbating mucosal injuries. However, the pathogenic CD4+ T cell subset involved in gastritis and the potential regulators are still unclear. Here we identified an IL-21-producing gastric CD4+T cell subset, which exhibited tissue-resident CXCR5−BTLA−PD-1hi TFH-like phenotype in H. pylori-positive gastritis patients. Meanwhile, we identified glucocorticoid-induced tumor necrosis factor receptor (GITR) as an important regulator to facilitate IL-21 production by CD4+T cells and accelerate mucosal inflammation in gastritis patients with H. pylori infection. Moreover, GITR expression was increased in gastric CD4+T cells of gastritis patients compared to healthy controls, along with the upregulated expression of its ligand GITRL in mucosal macrophages (Mϕ) of gastritis patients. Further observations showed that the activation of GITR/GITRL signal promoted the IL-21 production of CD4+T cells via the STAT3 pathway. Besides this, IL-21 from CD4+T cells induced the proliferation of B cell and promoted the production of inflammatory cytokines IL-1β and IL-6 and chemokines MIP-3α and CCL-25 as well as matrix metalloproteinase (MMP)-3 and MMP-9 by human gastric epithelial cells, suggesting the facilitating effect of IL-21-producing CD4+T cells on mucosal inflammation and injuries. Taking these data together, we revealed that GITR/GITRL signal promoted the polarization of mucosal IL-21-producing CD4+T cells in H. pylori-positive gastritis, which may provide therapeutic strategies for the clinical treatment of H. pylori-induced gastritis.

Association of Platelet Desialylation and Circulating Follicular Helper T Cells in Patients With Thrombocytopenia

“…Importantly, we show the strong positive correlation between elevation of circulating TFHs and desialylated platelets, supporting TFHs as a critical mediator in synergy to promote platelet desialylation. A recent study found that H. Pylori infection may lead to the upregulation of TFHs in gastritis patients ( 41 ), and several recent reports revealed an association between H. Pylori infection and the incidence of ITP ( 42 – 44 ). Hence, we speculate that H. Pylori may be related to the abnormally elevated TFHs in the infected individuals with ITP in the present study.…”

FGL1-LAG3 axis impairs IL-10-Producing regulatory T cells associated with Systemic lupus erythematosus disease activity

“…The real-time PCR was performed as previously described [ 31 ]. Total RNA was isolated using TRIzol reagent (Invitrogen, USA) according to the manufacturer's recommendations.…”

Clinical analysis of the effect of helicobacter pylori infection on immune function in children with peptic ulcer

“…The increase of CD4 + T lymphocyte level has a close relationship with the injury of gastric mucosa caused by Hp infection. 15 Moreover, CD4+T cells may function significantly in regulating or inhibiting CD8 + T cells, and CD8 + T cells may mediate more serious diseases in the absence of CD4 + T cells. 16 There would be obvious increase in the levels of CD4 + and CD8 + T lymphocytes in peripheral blood of children with Hp infection.…”