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Immunity. 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.

Author information

  • 1Department of Neurology, Ruhr-University Bochum, 44801 Bochum, Germany. Electronic address: aiden.haghikia@rub.de.
  • 2Department of Neurology, Friedrich-Alexander-University Erlangen-Nuremberg, 91054 Erlangen, Germany.
  • 3Department of Neurology, Ruhr-University Bochum, 44801 Bochum, Germany.
  • 4Medical Proteom-Center, Ruhr-University Bochum, 44801 Bochum, Germany.
  • 5Experimental and Clinical Research Center & Max-Delbrück Center Berlin, 13125 Berlin, Germany.
  • 6Institute for Food Toxicology and Analytical Chemistry, University of Veterinary Medicine Hannover, 30559 Hannover, Germany.
  • 7Institute for Food Toxicology and Analytical Chemistry, University of Veterinary Medicine Hannover, 30559 Hannover, Germany; Department of Food Chemistry, University of Wuppertal, 42097 Wuppertal, Germany.
  • 8Department of Human Genetics, Ruhr-University Bochum, 44801 Bochum, Germany.
  • 9Translational Immunology, Medical Faculty Carl Gustav Carus, TU Dresden, 01307 Dresden, Germany.
  • 10Integrative Metabolomics and Proteomics, Berlin Institute of Medical Systems Biology/Max-Delbrück Center for Molecular Medicine, 13125 Berlin, Germany.
  • 11Department of Neurology, Friedrich-Alexander-University Erlangen-Nuremberg, 91054 Erlangen, Germany. Electronic address: ralf.linker@uk-erlangen.de.

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.

PMID:
26488817
DOI:
10.1016/j.immuni.2015.09.007
[PubMed - indexed for MEDLINE]
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