Cited by 927T-cell and B-cell ImmunologyMultiple Sclerosis Research StudiesGut microbiota and health

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

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Haghikia, Aiden, Jörg, Stefanie, Duscha, Alexander, Berg, Johannes, Manzel, Arndt, Waschbisch, Anne, Hammer, Anna, Lee, De-Hyung +14 more·2015·Immunity

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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Crossref · 10.1016/j.immuni.2015.09.007

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Authors
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., & Linker, R. A.
Affiliations
  • Ruhr University Bochum (DE)
  • Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
  • Max Delbrück Center (DE)
  • University of Veterinary Medicine Hannover, Foundation (DE)
  • University of Wuppertal (DE)
  • Technische Universität Dresden (DE)
Corresponding author
  • Haghikia, Aiden
  • Linker, Ralf A.
Venue
Immunity
Publisher
Elsevier BV
Published
2015-10
Volume
43
Issue
4
Pages
817-829
ISSN
1074-7613 (ISSN-L)
OpenAlex
W1941562583
Cited by
927
References
35
Citations by year
2026: 54 · 2025: 103 · 2024: 109 · 2023: 99 · 2022: 122 · 2021: 110 · 2020: 89 · 2019: 77 · 2018: 73 · 2017: 58 · 2016: 28 · 2015: 4
FWCI
26.73
Type
journal article
Language
en
Update notices
erratum (2016-04-19)
Open access
Locations
  • Immunity (publishedVersion)
  • PubMed (publishedVersion)
  • MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (submittedVersion)
Funders
  • Novartis Foundation
  • Deutsche Forschungsgemeinschaft
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
Keywords
dietary fatty acids, long-chain fatty acids, short-chain fatty acids, central nervous system autoimmunity, experimental autoimmune encephalomyelitis, multiple sclerosis, Th1 cells, Th17 cells, regulatory T cells, p38 MAPK pathway, JNK1, lamina propria, gut microbiota metabolites
MeSH terms
Gastrointestinal Microbiome, Fecal Microbiota Transplantation, Liver X Receptors, Animals, Central Nervous System, Dietary Fats, Duodenum, Encephalomyelitis, Autoimmune, Experimental, Fatty Acids, Gene Expression Regulation, Lauric Acids, Molecular Weight, Spleen, Autoimmunity, T-Lymphocyte Subsets, Th1 Cells, MAP Kinase Signaling System, Lymphopoiesis, Receptors, G-Protein-Coupled, T-Lymphocytes, Regulatory, Mice, Orphan Nuclear Receptors, Th17 Cells, Transcriptome

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