Genetic and commensal induction of IL-18 drive intestinal epithelial MHCII via IFNγ.

ABSTRACT: Major histocompatibility complex class II (MHCII) is dynamically expressed on intestinal epithelial cells (IECs) throughout the intestine, but its regulation remains poorly understood. We observed that spontaneous upregulation of IEC MHCII in locally bred Rag1^-/- mice correlated with serum Interleukin (IL)-18, was transferrable via co-housing to commercially bred immunodeficient mice and could be inhibited by both IL-12 and IL-18 blockade. Overproduction of intestinal IL-18 due to an activating Nlrc4 mutation upregulated IEC MHCII via classical inflammasome machinery independently of immunodeficiency or dysbiosis. Immunodeficient dysbiosis increased Il-18 transcription, which synergized with NLRC4 inflammasome activity to drive elevations in serum IL-18. This IL-18-MHCII axis wa

SUBMITTER: Van Der Kraak LA 

PROVIDER: S-EPMC8562907 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature