Journal Article

The activity of the aryl hydrocarbon receptor in T cells tunes the gut microenvironment to sustain autoimmunity and neuroinflammation

Beiter, Rebecca M., Rivet-Noor, Courtney, Cahill, Hannah J., Brown, Lucille C., Brown, Ryan M., Olgun, Deniz G., Gaultier, Alban, Merchak, Andrea R., Slogar, Erica R.

2023

Overview

Multiple sclerosis (MS) is a T cell-driven autoimmune disease that attacks the myelin of the central nervous system (CNS) and currently has no cure. MS etiology is linked to both the gut flora and external environmental factors but this connection is not well understood. One immune system regulator responsive to nonpathogenic external stimuli is the aryl hydrocarbon receptor (AHR). The AHR, which binds diverse molecules present in the environment in barrier tissues, is a therapeutic target for MS. However, AHR’s precise function in T lymphocytes, the orchestrators of MS, has not been described. Here, we show that in a mouse model of MS, T cell-specific Ahr knockout leads to recovery driven by a decrease in T cell fitness. At the mechanistic level, we demonstrate that the absence of AHR changes the gut microenvironment composition to generate metabolites that impact T cell viability, such as bile salts and short chain fatty acids. Our study demonstrates a newly emerging role for AHR in mediating the interdependence between T lymphocytes and the microbiota, while simultaneously identifying new potential molecular targets for the treatment of MS and other autoimmune diseases.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Analysis / Animals / Antigens / Apoptosis / Aromatic compounds / Autoimmune Diseases / Autoimmunity / Biology and Life Sciences / Care and treatment / Cell viability / Cells / Central nervous system / Cytokines / Encephalomyelitis / Environmental factors / Etiology / External stimuli / Fatty acids / Flow cytometry / Hydrocarbons / Identification and classification / Immune system / Inflammation / Intestinal microflora / Ligands / Lymphocytes / Lymphocytes T / Medicine and Health Sciences / Metabolites / Mice / Microbiota / Microbiota (Symbiotic organisms) / Microenvironments / Multiple Sclerosis / Myelin / Neuroinflammatory Diseases / Pathology / Properties / Receptors / Receptors, Aryl Hydrocarbon - genetics / Receptors, Aryl Hydrocarbon - metabolism / Research and Analysis Methods / Spinal cord / Stains & staining / T cells / T-Lymphocytes / Therapeutic targets / Transcription factors / Weaning