Group 2 Innate Lymphoid Cells Are Involved in Skewed Type 2 Immunity of Gastric Diseases Induced by Helicobacter pylori Infection

Abstract

H. pylori induces a complicated local and systematic immune response and contributes to the carcinogenesis of gastric cancer. A primary type 1 immune response is evoked by H. pylori since its occurrence. However, it is not unusual that an inhibitory immunity is dominant in H. pylori-associated diseases, which are promoted by the formation of immunosuppressive microenvironment. But whether group 2 innate lymphoid cells (ILC2s) plays a critical role in H. pylori-induced skewed type 2 immunity is still unclear. In the present study, firstly, we confirmed that type 1 immunity was inhibited and type 2 immunity were undisturbed or promoted after H. pylori infection in vitro and in vivo. Secondly, GATA-3 was firstly found to be increased in the interstitial lymphocytes from H. pylori-associated gastric cancer, among them, Lin−GATA-3+ cells and Lin+GATA-3+ cells were also found to be enhanced, which indicated an important role for ILC2s in H. pylori infection. More importantly, ILC2s were found to be increased after H. pylori infection in clinical patients and animal models. In conclusion, our results indicated that ILC2-mediated innate immune response might play a potential role in dominant type 2 phenotype and immunosuppressive microenvironment in H. pylori infection.

Group 2 Innate Lymphoid Cells (ILC2): Type 2 Immunity and Helminth Immunity

“…It is still unknown whether there are generalized suppressive mechanisms to limit ILC2 activation, such as regulatory ILCs (ILCregs) that produce IL-10, or conversion into different types by cytokines such as IL-27 and IL-12. These considerations are quite important due to the major role of ILC2 in the context of health and disease [12,34]. In particular, understanding how ILC2s are regulated in the context of a helminth infection will be necessary for improving existing anthelmintic drugs and developing new therapeutics to treat helminth infections.…”

The interaction of intestinal microbiota and innate lymphoid cells in health and disease throughout life

“…Li et al . reported an increase in Lin + GATA3 + as well as Lin − GATA3 + ILC2‐like populations together with a more pronounced type 2 signature limiting the protective type 1 immune response in the development of cancers . In mice , Helicobacter typhlonius infection triggers IL‐17A expressing ILCs by synergizing DCs derived TNF‐α and IL‐23 in the Tbx21 −/− Rag2 −/− ulcerative colitis (TRUC) model …”

Helicobacter Pylori Induces GATA3-Dependent Chitinase 3 Like 1 (CHI3L1) Upregulation and Contributes to Vascular Endothelial Injuries

“…We then investigated which elements of the conceivable molecule mechanism H. pylori brought to vascular endothelial cells. According to our previous study, an increased expression of GATA3 induced by H. pylori might participate in skewed type-2 immune responses [35], which suggested that the increase of GATA3, induced by H. pylori , has the potential to effect more than just the stomach. Reduced GATA3 levels of Th2 responses induced a regression of atherosclerosis and other inflammatory diseases [18,36].…”