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

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

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoimmunity / drug effects*
  • Central Nervous System / immunology*
  • Dietary Fats / pharmacology*
  • Dietary Fats / toxicity
  • Duodenum / immunology*
  • Duodenum / metabolism
  • Duodenum / microbiology
  • Encephalomyelitis, Autoimmune, Experimental / etiology*
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Encephalomyelitis, Autoimmune, Experimental / metabolism
  • Fatty Acids / chemistry
  • Fatty Acids / pharmacology*
  • Fatty Acids / toxicity
  • Fecal Microbiota Transplantation
  • Gastrointestinal Microbiome / physiology
  • Gene Expression Regulation / immunology
  • Lauric Acids / toxicity
  • Liver X Receptors
  • Lymphopoiesis / drug effects*
  • MAP Kinase Signaling System
  • Mice
  • Molecular Weight
  • Orphan Nuclear Receptors / biosynthesis
  • Orphan Nuclear Receptors / genetics
  • Receptors, G-Protein-Coupled / biosynthesis
  • Receptors, G-Protein-Coupled / genetics
  • Spleen / immunology
  • Spleen / pathology
  • T-Lymphocyte Subsets / drug effects*
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocytes, Regulatory / immunology
  • Th1 Cells / immunology
  • Th17 Cells / immunology
  • Transcriptome

Substances

  • Dietary Fats
  • Fatty Acids
  • Lauric Acids
  • Liver X Receptors
  • Orphan Nuclear Receptors
  • Receptors, G-Protein-Coupled
  • lauric acid