Abstract
Inflammatory bowel disease (IBD) is a multifactorial disease involving defective immune responses against invasive microbiota. Genes associated with innate immune responses to microbes have been highlighted in the pathogenesis of IBD. To determine the role of Rab32 in the pathogenesis of IBD, we administered dextran sodium sulfate (DSS) to CD11c(+) cell-specific Rab32 knockout (CD11c-Cre(+)Rab32(f/f)) mice to induce colitis. Rab32 deficiency in CD11c(+) cells resulted in more severe disease progression and increased mortality. Histopathological analysis showed extensive damage to the colon mucosa in DSS-treated CD11c-Cre(+)Rab32(f/f) mice, including more severe damage to the epithelial layer and crypts, as well as more inflammatory cell infiltration. The pro-inflammatory cytokines IL1A, IL1B, IL6, and CSF3 and chemokines CXCL1 and CXCL2 were significantly increased, and the frequency of CD11b(+)Ly6G(+) neutrophils was higher in CD11c-Cre(+)Rab32(f/f) colitis mice. Furthermore, CD11c(+) cells deficient for Rab32 exhibited a significant increase in bacterial translocation in inflamed colon tissue. The present data demonstrate that Rab32 knockout in CD11c(+) cells aggravates the development of DSS-induced colitis and suggest that the Rab32-related antimicrobial pathway is involved in the pathogenesis of IBD.