Abstract
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.
Highlights
Mucosal-associated invariant T (MAIT) cells are a class of innate-like T cells that recognize the small-molecule derivatives produced by microbes during riboflavin synthesis [1, 3, 4]
To explore the relation of IL-9 with Mucosal associated invariant T (MAIT) cells, we further analyzed the percentage of IL-9+ MAIT cells and the correlation between the percentage of MAIT cells and serum IL-9 level in H. pylori gastritis patients
Immunofluorescence assay showed that the co-localization of IL-9 with MAIT cells were increased in the gastric mucosa from H. pylori gastritis patients, and the percentage of MAIT cells in the mucosa was positively correlated with the concentration of serum IL9 (Figures 1D,E)
Summary
Mucosal-associated invariant T (MAIT) cells are a class of innate-like T cells that recognize the small-molecule derivatives produced by microbes during riboflavin synthesis [1, 3, 4]. Changed frequencies of MAIT cell in peripheral blood and mucosal tissues are observed in a variety of inflammatory diseases, including autoimmune diseases [9], type diabetes (T1D) [10], type 2 diabetes (T2D) [11], rheumatoid arthritis [12], and gastritis [2]. MAIT cells are observed to localize in proximity to H. pylori in the human gastric mucosa [2]. Upon the recognition of H. pylori infected macrophage, MAIT cells can produce cytokines and exhibit cytotoxic activity [19]. The function of MAIT cells and regulatory factors in H. pylori gastritis are not fully clarified
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