| Autor: |
Merchak, Andrea R., Cahill, Hannah J., Brown, Lucille C., Brown, Ryan M., Rivet-Noor, Courtney, Beiter, Rebecca M., Slogar, Erica R., Olgun, Deniz G., Gaultier, Alban |
| Předmět: |
|
| Zdroj: |
PLoS Biology; 2/14/2023, Vol. 21 Issue 2, p1-24, 24p, 6 Graphs |
| Abstrakt: |
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. Multiple sclerosis is a T cell-driven autoimmune disease that is linked to both gut flora and external environmental factors. This study shows that deleting the aryl hydrocarbon receptor (a sensor for the gut microbiota) in T lymphocytes triggers a change in intestinal bile acids and short chain fatty acids, which appear to protect against multiple sclerosis. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
|
|
Nepřihlášeným uživatelům se plný text nezobrazuje |
K zobrazení výsledku je třeba se přihlásit.
|
