T cell AHR activity tunes the Gut Microenvironment to Sustain Autoimmunity [sephouse_feces]

The contribution of the environment and, in particular, the gut flora to multiple sclerosis (MS) etiology is well documented but not well understood. The aryl hydrocarbon receptor (AHR) binds numerous molecules present in the environment and is a therapeutic target for MS: however, its precise function in T lymphocytes, the orchestrators of MS, has not been described. Here, we show that CD4 specific Ahr knockout drives recovery in an animal model of MS driven by a decrease in T cell fitness. At the mechanistic level, we show that the absence of AHR changes the gut microenvironment composition to generate metabolites, such as bile salts and short chain fatty acids, that impact T cell viability. Our study demonstrates a newly emerging role for AHR in mediating the interdependence between T lymphocytes and the microbiota while identifying new potential molecular targets for the treatment of MS and other autoimmune diseases. Microbiome comparative analysis via 16S sequencing of feces of separatly housed Cd4creAhrfl/fl and Ahrfl/fl mice.