SYK-CARD9 Signaling Axis Promotes Gut Fungi-Mediated Inflammasome Activation to Restrict Colitis and Colon Cancer.

ABSTRACT: Fungi represent a significant proportion of the gut microbiota. Aberrant immune responses to fungi are frequently observed in inflammatory bowel diseases (IBD) and colorectal cancer (CRC), and mutations in the fungal-sensing pathways are associated with the pathogenesis of IBD. Fungal recognition receptors trigger downstream signaling via the common adaptor protein CARD9 and the kinase SYK. Here we found that commensal gut fungi promoted inflammasome activation during AOM-DSS-induced colitis. Myeloid cell-specific deletion of Card9 or Syk reduced inflammasome activation and interleukin (IL)-18 maturation and increased susceptibility to colitis and CRC. IL-18 promoted epithelial barrier restitution and interferon-γ production by intestinal CD8⁺ T cells. Supplementation of IL-18 o

SUBMITTER: Malik A 

PROVIDER: S-EPMC6541497 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature