OX4OL/OX40 Signal Promotes IL-9 Production by Mucosal MAIT Cells During Helicobacter pylori Infection

Ming, Siqi1,2,3; Zhang, Mei1; Liang, Zibin4; Li, Chunna5; He, Jianzhong6; Chen, Peiyu1; Zhang, Shunxian1; Niu, Xiaoli2; Deng, Shimei2; Geng, Lanlan1; Zhang, Guoliang3; Gong, Sitang1; Wu, Yongjian1,2

2021-03-11

10.3389/fimmu.2021.626017

Frontiers in Immunology   影响因子和分区

1664-3224

Mucosal associated invariant T (MAIT) cells play a critical role in Helicobacter pylori (H. pylori)-induced gastritis by promoting mucosal inflammation and aggravating mucosal injuries (1, 2). However, the underlying mechanism and key molecules involved are still uncertain. Here we identified OX40, a co-stimulatory molecule mainly expressed on T cells, as a critical regulator to promote proliferation and IL-9 production by MAIT cells and facilitate mucosal inflammation in H. pylori-positive gastritis patients. Serum examination revealed an increased level of IL-9 in gastritis patients. Meanwhile, OX40 expression was increased in mucosal MAIT cells, and its ligand OX40L was also up-regulated in mucosal dendritic cells (DCs) of gastritis patients, compared with healthy controls. Further results demonstrated that activation of the OX40/OX40L pathway promoted IL-9 production by MAIT cells, and MAIT cells displayed a highly-activated phenotype after the cross-linking of OX40 and OX40L. Moreover, the level of IL-9 produced by MAIT cells was positively correlated with inflammatory indexes in the gastric mucosa, suggesting the potential role of IL-9-producing MAIT cells in mucosal inflammation. Taken together, we elucidated that OX40/OX40L axis promoted mucosal MAIT cell proliferation and IL-9 production in H. pylori-induced gastritis, which may provide potential targeting strategies for gastritis treatment.

MAIT cells H. pylori gastritis IL-9 inflammation OX40

SCI

英语

通讯

National Natural Science Foundation of China[81770552,81801571] ; China Postdoctoral Science Foundation[2020T130131] ; Development Project of Foshan Fourth People's Hospital[FSSYKF-2020017] ; Medical Science and Technology Research Fund of Guangdong[A2019326] ; Shenzhen Scientific and Technological Foundation[JCYJ20180228162336873]

Immunology

Immunology

WOS:000632220200001

FRONTIERS MEDIA SA

Web of Science

1.Guangzhou Med Univ, Guangzhou Inst Pediat, Guangzhou Women & Childrens Med Ctr, Dept Gastroenterol,Affiliated Hosp 6,Qingyuan Peo, Guangzhou, Peoples R China
2.Sun Yat Sen Univ, Zhongshan Sch Med, Affiliated Hosp 5, Ctr Infect & Immun, Guangzhou, Peoples R China
3.Southern Univ Sci & Technol, Peoples Hosp Shenzhen 3, Natl Clin Res Ctr Infect Dis, Affiliated Hosp 2, Shenzhen, Peoples R China
4.Sun Yat Sen Univ, Dept Thorac Oncol, Ctr Canc, Affiliated Hosp 5, Zhuhai, Peoples R China
5.Sun Yat Sen Univ, Dept Infect Dis, Affiliated Hosp 5, Zhuhai, Peoples R China
6.Sun Yat Sen Univ, Dept Pathol, Affiliated Hosp 5, Zhuhai, Peoples R China

Ming, Siqi,Zhang, Mei,Liang, Zibin,et al. OX4OL/OX40 Signal Promotes IL-9 Production by Mucosal MAIT Cells During Helicobacter pylori Infection[J]. Frontiers in Immunology,2021,12.

Ming, Siqi.,Zhang, Mei.,Liang, Zibin.,Li, Chunna.,He, Jianzhong.,...&Wu, Yongjian.(2021).OX4OL/OX40 Signal Promotes IL-9 Production by Mucosal MAIT Cells During Helicobacter pylori Infection.Frontiers in Immunology,12.

Ming, Siqi,et al."OX4OL/OX40 Signal Promotes IL-9 Production by Mucosal MAIT Cells During Helicobacter pylori Infection".Frontiers in Immunology 12(2021).