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.