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Dietary fatty acids directly impact central nervous system autoimmunity via the small intestine

Item Type:Article
Title:Dietary fatty acids directly impact central nervous system autoimmunity via the small intestine
Creators Name:Haghikia, A. and Joerg, S. and Duscha, A. and Berg, J. and Manzel, A. and Waschbisch, A. and Hammer, A. and Lee, D.H. and May, C. and Wilck, N. and Balogh, A. and Ostermann, A.I. and Schebb, N.H. and Akkad, D.A. and Grohme, D.A. and Kleinewietfeld, M. and Kempa, S. and Thoene, J. and Demir, S. and Mueller, D.N. and Gold, R. and Linker, R.A.
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.
Keywords:Autoimmunity, Central Nervous System, Dietary Fats, Duodenum, Experimental Autoimmune Encephalomyelitis, Fatty Acids, Fecal Microbiota Transplantation, G-Protein-Coupled Receptors, Gastrointestinal Microbiome, Gene Expression Regulation, Lauric Acids, Lymphopoiesis, MAP Kinase Signaling System, Molecular Weight, Orphan Nuclear Receptors, Regulatory T-Lymphocytes, Spleen, T-Lymphocyte Subsets, Th1 Cells, Th17 Cells, Transcriptome, Animals, Mice
Source:Immunity
ISSN:1074-7613
Publisher:Cell Press / Elsevier (U.S.A.)
Volume:43
Number:4
Page Range:817-829
Date:20 October 2015
Additional Information:Correction in: Immunity 44(4): 951-953
Official Publication:https://doi.org/10.1016/j.immuni.2015.09.007
PubMed:View item in PubMed

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