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

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Item Type:	Article
Title:	Dietary fatty acids directly impact central nervous system autoimmunity via the small intestine
Creators Name:	Haghikia, A., Jörg, S., Duscha, A., Berg, J., Manzel, A., Waschbisch, A., Hammer, A., Lee, D.H., May, C., Wilck, N., Balogh, A., Ostermann, A.I., Schebb, N.H., Akkad, D.A., Grohme, D.A., Kleinewietfeld, M., Kempa, S., Thöne, J., Demir, S., Müller, D.N., 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
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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