Silk fibroin hydrogel as mucosal vaccine carrier: induction of gastric CD4+TRM cells mediated by inflammatory response induces optimal immune protection against Helicobacter felis

Tissue-resident memory T (T(RM)) cells, located in the epithelium of most peripheral tissues, constitute the first-line defense against pathogen infections. Our previous study reported that gastric subserous layer (GSL) vaccination induced a “pool” of protective tissue-resident memory CD4+T (CD4+T(RM)) cells in the gastric epithelium. However, the mechanistic details how CD4+T(RM) cells form in the gastric epithelium are unknown. Here, our results suggested that the vaccine containing CCF in combination with Silk fibroin hydrogel (SF) broadened the distribution of gastric intraepithelial CD4+T(RM) cells. It was revealed that the gastric intraepithelial T(RM) cells were even more important than circulating memory T cells against infection by Helicobacter felis. It was also shown that gastric-infiltrating neutrophils were involved as indispensable mediators which secreted CXCL10 to chemoattract CXCR3+CD4+T cells into the gastric epithelium. Blocking of CXCR3 or neutrophils significantly decreased the number of gastric intraepithelial CD4+T(RM) cells due to reduced recruitment of CD4+T cells. This study demonstrated the protective efficacy of gastric CD4+T(RM) cells against H. felis infection, and highlighted the influence of neutrophils on gastric intraepithelial CD4+T(RM) cells formation.