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

Ming，Siqi1; Yin，Huan2; Li，Xingyu2; Gong，Sitang3; Zhang，Guoliang4; Wu，Yongjian2,3

2021-09-10

10.3389/fimmu.2021.736269

Frontiers in Immunology   影响因子和分区

1664-3224

1664-3224

Gastric CD4T 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 CD4T cell subset, which exhibited tissue-resident CXCR5BTLAPD-1 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 CD4T cells and accelerate mucosal inflammation in gastritis patients with H. pylori infection. Moreover, GITR expression was increased in gastric CD4T 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 CD4T cells via the STAT3 pathway. Besides this, IL-21 from CD4T 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 CD4T cells on mucosal inflammation and injuries. Taking these data together, we revealed that GITR/GITRL signal promoted the polarization of mucosal IL-21-producing CD4T cells in H. pylori-positive gastritis, which may provide therapeutic strategies for the clinical treatment of H. pylori-induced gastritis.

gastritis GITR H. pylori IL-21 TFH-like cells

SCI

英语

第一

National Natural Science Foundation of China[81770552,81801571,82102249] ; China Postdoctoral Science Foundation[2020T130131] ; National Key Research and Development Plan[2019YFC0840602] ; Guangdong Scientific and Technological Foundation["2020B1111170014","2019A1515110055"] ; Shenzhen Scientific and Technological Foundation["KCXFZ202002011007083","JCYJ20180228162321234"]

Immunology

Immunology

WOS:000703807200001

FRONTIERS MEDIA SA

2-s2.0-85115875008

Scopus

1.National Clinical Research Center for Infectious Diseases,Shenzhen Third People’s Hospital,Southern University of Science and Technology,Shenzhen,China
2.Center for Infection and Immunity,Hospital of Sun Yat-sen University,Zhuhai,China
3.Department of Gastroenterology,Guangzhou Institute of Pediatrics,Guangzhou Women and Children’s Medical Center,Guangzhou Medical University,Guangzhou,China
4.

Ming，Siqi,Yin，Huan,Li，Xingyu,et al. GITR Promotes the Polarization of TFH-Like Cells in Helicobacter pylori-Positive Gastritis[J]. Frontiers in Immunology,2021,12.

Ming，Siqi,Yin，Huan,Li，Xingyu,Gong，Sitang,Zhang，Guoliang,&Wu，Yongjian.(2021).GITR Promotes the Polarization of TFH-Like Cells in Helicobacter pylori-Positive Gastritis.Frontiers in Immunology,12.

Ming，Siqi,et al."GITR Promotes the Polarization of TFH-Like Cells in Helicobacter pylori-Positive Gastritis".Frontiers in Immunology 12(2021).