Enteric glial cells express type II major histocompatibility complex (MHC-II) molecules in Crohn’s disease and Chagas disease, but it is unclear whether the expressed molecules are functional. We examined the capabilities of enteric glia to act as an antigen presenting cell in vivo and whether glial MHC-II has immunomodulatory effects.
We generated Sox10;IAB mice to ablate MHC-II in enteric glia following exposure to tamoxifen. We measured phagocytic activity and autophagy activation to assess potential peptide sources loaded onto glial MHC-II and measured T- and B-lymphocyte activation and serum and colonic tissue cytokine levels to study enteric glial immunomodulatory capabilities.
Enteric glia express MHC-II molecules in response to a subclinical dose of IFNγ and LPS in vivo. Glial MHC-II expression contributes to effective B-lymphocyte and T-lymphocyte activation with marked effects on T17 and T subtypes. No effect on T1 or T2 subtypes was observed. Enteric glial MHC-II does not have a major effect on serum or colonic tissue cytokine levels but may influence local cytokine levels. Glial MHC-II expression requires the activation of autophagy pathways but activating autophagy alone is not sufficient to drive glial MHC-II expression.
Enteric glia express MHC-II as a mechanism to tune intestinal immune responses. Glial autophagy is triggered in response to proinflammatory stimuli and induces glial antigen presentation, which functions to modulate the activation of T-lymphocyte subsets involved in tolerance. These observations suggest that enteric glia may express MHC-II to maintain immune homeostasis during inflammatory conditions such as Crohn’s disease.

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