Dietary Fatty Acids Directly Impact Central Nervous System Autoimmunity via the Small Intestine
Aiden Haghikia, Stefanie Jörg, Alexander Duscha, Johannes Berg, Arndt Manzel, Anne Waschbisch, Anna Hammer, De-Hyung Lee, Caroline May, Nicola Wilck, Andras Balogh, Annika I Ostermann, Nils Helge Schebb, Denis A Akkad, Diana A Grohme, Markus Kleinewietfeld, Stefan Kempa, Jan Thöne, Seray Demir, Dominik N Müller, Ralf Gold, Ralf A Linker, Aiden Haghikia, Stefanie Jörg, Alexander Duscha, Johannes Berg, Arndt Manzel, Anne Waschbisch, Anna Hammer, De-Hyung Lee, Caroline May, Nicola Wilck, Andras Balogh, Annika I Ostermann, Nils Helge Schebb, Denis A Akkad, Diana A Grohme, Markus Kleinewietfeld, Stefan Kempa, Jan Thöne, Seray Demir, Dominik N Müller, Ralf Gold, Ralf A Linker
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.
Copyright © 2015 Elsevier Inc. All rights reserved.
Source: PubMed