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Comparative Study
. 2015 Oct 20;43(4):817-29.
doi: 10.1016/j.immuni.2015.09.007.

Dietary Fatty Acids Directly Impact Central Nervous System Autoimmunity via the Small Intestine

Aiden Haghikia  1 , Stefanie Jörg  2 , Alexander Duscha  3 , Johannes Berg  3 , Arndt Manzel  2 , Anne Waschbisch  2 , Anna Hammer  2 , De-Hyung Lee  2 , Caroline May  4 , Nicola Wilck  5 , Andras Balogh  5 , Annika I Ostermann  6 , Nils Helge Schebb  7 , Denis A Akkad  8 , Diana A Grohme  9 , Markus Kleinewietfeld  9 , Stefan Kempa  10 , Jan Thöne  3 , Seray Demir  3 , Dominik N Müller  5 , Ralf Gold  3 , Ralf A Linker  11
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Free article
Comparative Study

Dietary Fatty Acids Directly Impact Central Nervous System Autoimmunity via the Small Intestine

Aiden Haghikia et al. Immunity. .
Free article

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Abstract

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 autoimmunity to 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 autoimmune diseases such as multiple sclerosis.

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