CD38 and extracellular NAD+ regulate the development and maintenance of Hp vaccine-induced CD4+ TRM in the gastric epithelium

Tissue-resident memory T cells (T_RM) can be induced by Infection and vaccination, and play a key role in maintaining long-term protective immunity against mucosal pathogens. Our studies explored the key factors and mechanisms affecting the differentiation, maturation, and stable residence of gastric epithelial CD4⁺ T_RM induced by Helicobacter pylori (Hp) vaccine and optimized Hp vaccination to promote the generation and residence of T_RM. Cluster of differentiation (CD)38 regulated mitochondrial activity and enhanced Transforming Growth Factor-β signal transduction to promote the differentiation and residence of gastric epithelial CD4⁺ T_RM by mediating the expression of CD105. Extracellular nucleotides influenced the long-term maintenance of T_RM in gastric epithelium by the P2X7 Receptor (P2RX7). Vitamin D3 and Gram-positive enhancer matrix (GEM) particles as immune adjuvants combined with Hp vaccination promoted the production of CD69⁺CD103⁺CD4⁺ T_RM.