Aiden Haghikia, Stefanie Jorg, Alexander Duscha, Johannes Berg, Arndt Manzel, Anne Waschbisch, Anna Hammer, De-Hyung Lee, Caroline May, Nicola Wilck, Andras Balogh, Annika I. Ostermann,
Nils Helge Schebb, Denis A. Akkad, Diana A. Grohme, Markus Kleinewietfeld, Stefan Kempa, Jan Thone, Seray Demir, Dominik N. Muller, Ralf Gold, and Ralf A. Linker
Growing empirical evidence suggests that nutrition and bacterial metabolites might impact the systemic immune response in the context of disease and auto- immunity. 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 patogenic Th1 and/or Th17 cell populations in the small intestine. Treatment with SCFAs ameliorated EAE and reduced axonal damage via long-lasting imprinting on laminapropria-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.