Dietary Fatty Acids Directly Impact Central Nervous System Autoimmunity via the Small Intestine
2015
Growing empirical evidence suggests that nutrition and bacterial metabolites might impact the systemic immune response in the context of disease and
autoimmunity. We report that
long-chain fatty acids(LCFAs) enhanced differentiation and proliferation of T helper 1 (Th1) and/or Th17 cells and impaired their intestinal sequestration via p38-MAPK pathway. Alternatively, dietary short-chain FAs (SCFAs) expanded gut T regulatory (Treg) cells by suppression of the JNK1 and p38 pathway. We used
experimental autoimmune encephalomyelitis(EAE) as a model of T cell-mediated
autoimmunityto show that LCFAs consistently decreased SCFAs in the gut and exacerbated disease by expanding pathogenic Th1 and/or Th17 cell populations in the small intestine. Treatment with SCFAs ameliorated EAE and reduced axonal damage via long-lasting imprinting on
lamina-propria-derived Treg cells. These data demonstrate a direct dietary impact on intestinal-specific, and subsequently central nervous system-specific, Th cell responses in
autoimmunity, and thus might have therapeutic implications for
autoimmunediseases such as multiple sclerosis.
Keywords:
-
Correction
-
Source
-
Cite
-
Save
36
References
413
Citations
NaN
KQI