Immune regulation via RegIII
The Reg gene family encodes a diverse group of secreted proteins, which are further classified into subgroups (I, II, III, IV) that contain conserved sequence motifs found in C-type lectin carbohydrate recognition domains (CRDs)100. Increased expression of RegIII is dependent on factors such as surgery, nutrition, and inflammation due to bacterial invasion or mucosal damage100-102. Additionally, RegIIIγ (the mouse homolog of human REG3α) expression is dependent on the microbiota as a study demonstrated a significant decrease in RegIIIγ expression in germ-free mice compared to wild-type mice100.
The C-type lectins of the RegIII family, secreted by enterocytes and Paneth cells primarily in the distal ileum, show bactericidal properties by restricting mucosal access of gram-positive bacteria to the small intestinal epithelium and by enabling spatial segregation59,103. This protection is achieved through TLRs, which detect the microorganisms and activate Myd88 signaling (Fig. 1D)59. Mice lacking Myd88 showed a dramatic increase in the bacterial number in the small intestine, compared to their wild-type littermates59. Additionally, in RegIIIγ knockout mice, the number of gram-positive bacteria increased in the small intestine compared to the wild-type littermates, but the gram-negative bacterial loads stayed the same59.