Dietary tryptophan links encephalogenicity of autoreactive T cells with gut microbial ecology.

Autor: Sonner JK; DKTK Clinical Cooperation Unit Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany.; Department of Neurology, Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany.; Institute of Neuroimmunology and Multiple Sclerosis, Center for Molecular Neurobiology Hamburg, University Hospital Hamburg-Eppendorf, Hamburg, Germany., Keil M; DKTK Clinical Cooperation Unit Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany., Falk-Paulsen M; Institute of Clinical Molecular Biology, University Kiel, Kiel, Germany., Mishra N; Institute of Clinical Molecular Biology, University Kiel, Kiel, Germany., Rehman A; Institute of Clinical Molecular Biology, University Kiel, Kiel, Germany., Kramer M; DKTK Clinical Cooperation Unit Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany.; Department of Neurology, Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany., Deumelandt K; DKTK Clinical Cooperation Unit Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany.; Department of Neurology, Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany.; Immatics Biotechnologies GmbH, Tübingen, Germany., Röwe J; DKTK Clinical Cooperation Unit Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany., Sanghvi K; DKTK Clinical Cooperation Unit Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany.; Department of Neurology, Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany., Wolf L; DKTK Clinical Cooperation Unit Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany.; Department of Neurology, Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany., von Landenberg A; DKTK Clinical Cooperation Unit Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany.; Department of Neurology, Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany., Wolff H; Molecular Biotechnology, Department of Biosciences and Buchmann Institute for Molecular Life Sciences (BMLS), Goethe-University Frankfurt, Frankfurt, Germany., Bharti R; Institute of Clinical Molecular Biology, University Kiel, Kiel, Germany., Oezen I; DKTK Clinical Cooperation Unit Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany., Lanz TV; DKTK Clinical Cooperation Unit Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany.; Division of Immunology and Rheumatology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA., Wanke F; University Medical Center of the Johannes Gutenberg-University Mainz, Institute for Molecular Medicine, Mainz, Germany.; Roche, Basel, Switzerland., Tang Y; University Medical Center of the Johannes Gutenberg-University Mainz, Institute for Molecular Medicine, Mainz, Germany.; Merck KGaA, Darmstadt, Germany., Brandao I; Center for Thrombosis and Hemostasis (CTH), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany., Mohapatra SR; Junior Group Brain Cancer Metabolism, German Cancer Research Center (DKFZ), Heidelberg, Germany., Epping L; University Hospital Münster, Department of Neurology with Institute of Translational Neurology, 48149, Münster, Germany., Grill A; Center for Thrombosis and Hemostasis (CTH), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany., Röth R; nCounter Core Facility, Institute of Human Genetics, University of Heidelberg, Heidelberg, Germany., Niesler B; nCounter Core Facility, Institute of Human Genetics, University of Heidelberg, Heidelberg, Germany., Meuth SG; University Hospital Münster, Department of Neurology with Institute of Translational Neurology, 48149, Münster, Germany., Opitz CA; Junior Group Brain Cancer Metabolism, German Cancer Research Center (DKFZ), Heidelberg, Germany.; Department of Neurology and National Center of Tumor Diseases (NCT), University Hospital Heidelberg, Heidelberg, Germany., Okun JG; CCU Children's Hospital and Metabolic Center Heidelberg, Heidelberg, Germany., Reinhardt C; Center for Thrombosis and Hemostasis (CTH), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany., Kurschus FC; University Medical Center of the Johannes Gutenberg-University Mainz, Institute for Molecular Medicine, Mainz, Germany.; Department of Dermatology, Heidelberg University Hospital, Heidelberg, Germany., Wick W; DKTK Clinical Cooperation Unit Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany., Bode HB; Molecular Biotechnology, Department of Biosciences and Buchmann Institute for Molecular Life Sciences (BMLS), Goethe-University Frankfurt, Frankfurt, Germany., Rosenstiel P; Institute of Clinical Molecular Biology, University Kiel, Kiel, Germany., Platten M; DKTK Clinical Cooperation Unit Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany. m.platten@dkfz-heidelberg.de.; Department of Neurology, Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany. m.platten@dkfz-heidelberg.de.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2019 Oct 25; Vol. 10 (1), pp. 4877. Date of Electronic Publication: 2019 Oct 25.
DOI: 10.1038/s41467-019-12776-4
Abstrakt: The interaction between the mammalian host and its resident gut microbiota is known to license adaptive immune responses. Nutritional constituents strongly influence composition and functional properties of the intestinal microbial communities. Here, we report that omission of a single essential amino acid - tryptophan - from the diet abrogates CNS autoimmunity in a mouse model of multiple sclerosis. Dietary tryptophan restriction results in impaired encephalitogenic T cell responses and is accompanied by a mild intestinal inflammatory response and a profound phenotypic shift of gut microbiota. Protective effects of dietary tryptophan restriction are abrogated in germ-free mice, but are independent of canonical host sensors of intracellular tryptophan metabolites. We conclude that dietary tryptophan restriction alters metabolic properties of gut microbiota, which in turn have an impact on encephalitogenic T cell responses. This link between gut microbiota, dietary tryptophan and adaptive immunity may help to develop therapeutic strategies for protection from autoimmune neuroinflammation.
Databáze: MEDLINE