Helicobacter pylori activates SLFN4+MDSCs to accelerate gastric intestinal metaplasia.

Chronic infection with Helicobacter pylori (H. pylori) is a major risk factor for gastric cancer. This work attempted to investigate the underlying mechanism of SLFN4+ myeloid-derived suppressor cells (MDSCs) in affecting gastric intestinal metaplasia (GIM). H. pylori infection enhanced the expression of IFN-α and SLFN4, and activated JAK2/STAT1 signaling pathway in bone marrow cells or mouse gastric corpus. Meanwhile, IFN-α induced the transportation of STAT1 to the nucleus and activated the SLFN4 promoter. Moreover, the proportion of SLFN4+MDSC was decreased in IFN-α-treated bone marrow cells following TB42 treatment (JAK2/STAT1 signaling inhibitor). Additionally, miR-130b-3p was secreted by SLFN4+MDSCs. MiR-130b-3p was upregulated, tuberous sclerosis complex 1 (TSC1) was downregulated in H. pylori + patients. MiR-130b-3p inhibition in SLFN4+MDSCs alleviated GIM. In conclusion, H. pylori infection-induced high levels of IFN-α activated JAK/STAT1 signaling pathway to promote differentiation of SLFN4+MDSCs. High expression of miR-130b-3p in SLFN4+MDSCs inactivated Shh signaling pathway by targeting TSC1, thereby promoting GIM.