Atg16l1 in dendritic cells is required for antibacterial defense and autophagy in murine colitis.

Abstract

Autophagy-related 16-like 1 (Atg16l1) contributes to the susceptibility to ulcerative colitis (UC). The functional consequences of Atg16l1 in UC pathogenesis are poorly understood. We aimed to confirm how Atg16l1 deficiency in dendritic cells (DCs) affects murine colitis development. Atg16l1f/f mice and mice with Atg16l1 deficiency in CD11c+ DCs (Atg16l1ΔDC ) were generated for colitis models induction. Disease activity index, weight loss, colon score/length, and histopathological analysis were assessed for colitis severity. Mononuclear cells from mesenteric lymph node (MLN) were extracted for CD44/CD69 measurement by flow cytometry. Bacterial cultures of MLN and stool homogenates were used to evaluate the bacterial translocation. Bone marrow-derived dendritic cells (BMDCs) were isolated and cultured for immunofluorescence of autophagy-related proteins. Atg16l1 knockout in CD11c+ DCs exacerbated intestinal inflammation of dextran sulfate sodium (DSS)-induced colitis in vivo. Atg16l1 deficiency in CD11c+ DCs had no effect on the expression of CD44 and CD69. Bacterial translocation showed that bacteria amount in MLN and stool of DSS-induced colitis with Atg16l1 deficiency significantly higher than that of control. Immunofluorescence revealed that Atg16l1 deficiency obviously inhibited co-expression of LC3 and Lamp1 with S. typhimurium, enhanced co-expression of rab5 and rab7 with S. typhimurium, while did not affect Beclin1. We confirmed that Atg16l1 deficiency in DCs exacerbated the intestinal inflammation of DSS-induced colitis. Atg16l1 deficiency in DCs promotes the bacterial translocation of DSS-induced colitis in vivo and regulates autophagy and phagocytosis in BMDCs. Findings provided a novel perspective to study UC pathogenesis.