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

doi:10.1016/j.immuni.2015.09.007

Comparative Study

. 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

Aiden Haghikia¹, Stefanie Jörg², Alexander Duscha³, Johannes Berg³, Arndt Manzel², Anne Waschbisch², Anna Hammer², De-Hyung Lee², Caroline May⁴, Nicola Wilck⁵, Andras Balogh⁵, Annika I Ostermann⁶, Nils Helge Schebb⁷, Denis A Akkad⁸, Diana A Grohme⁹, Markus Kleinewietfeld⁹, Stefan Kempa¹⁰, Jan Thöne³, Seray Demir³, Dominik N Müller⁵, Ralf Gold³, Ralf A Linker¹¹

Affiliations

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

PMID: 26488817
DOI: 10.1016/j.immuni.2015.09.007

Free article

Comparative Study

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

Aiden Haghikia et al. Immunity. 2015.

Free article

. 2015 Oct 20;43(4):817-29.

doi: 10.1016/j.immuni.2015.09.007.

Authors

Affiliations

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

PMID: 26488817
DOI: 10.1016/j.immuni.2015.09.007

Erratum in

Dietary Fatty Acids Directly Impact Central Nervous System Autoimmunity via the Small Intestine.
Haghikia A, Jörg S, Duscha A, Berg J, Manzel A, Waschbisch A, Hammer A, Lee DH, May C, Wilck N, Balogh A, Ostermann AI, Schebb NH, Akkad DA, Grohme DA, Kleinewietfeld M, Kempa S, Thöne J, Demir S, Müller DN, Gold R, Linker RA. Haghikia A, et al. Immunity. 2016 Apr 19;44(4):951-3. doi: 10.1016/j.immuni.2016.04.006. Immunity. 2016. PMID: 27096322 No abstract available.

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.

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Comment in

Short, but Smart: SCFAs Train T Cells in the Gut to Fight Autoimmunity in the Brain.
Bhutia YD, Ganapathy V. Bhutia YD, et al. Immunity. 2015 Oct 20;43(4):629-31. doi: 10.1016/j.immuni.2015.09.014. Immunity. 2015. PMID: 26488813 Free PMC article.
T cell responses: A long-chain reaction.
Minton K. Minton K. Nat Rev Immunol. 2015 Dec;15(12):726-7. doi: 10.1038/nri3934. Epub 2015 Oct 30. Nat Rev Immunol. 2015. PMID: 26515077 No abstract available.

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

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

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