Selection of cross-reactive T cells by commensal and food-derived yeasts drives cytotoxic T H 1 cell responses in Crohn's disease.

Autor: Martini GR; Institute of Immunology, Christian-Albrechts-University of Kiel and University Medical Center Schleswig-Holstein, Kiel, Germany.; Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel and University Medical Center Schleswig-Holstein, Kiel, Germany., Tikhonova E; Institute of Immunology, Christian-Albrechts-University of Kiel and University Medical Center Schleswig-Holstein, Kiel, Germany.; Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel and University Medical Center Schleswig-Holstein, Kiel, Germany., Rosati E; Institute of Immunology, Christian-Albrechts-University of Kiel and University Medical Center Schleswig-Holstein, Kiel, Germany.; Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel and University Medical Center Schleswig-Holstein, Kiel, Germany., DeCelie MB; The Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, Cornell University, New York, NY, USA.; Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medicine, Cornell University, New York, NY, USA.; Department of Microbiology and Immunology, Weill Cornell Medicine, Cornell University, New York, NY, USA., Sievers LK; Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel and University Medical Center Schleswig-Holstein, Kiel, Germany.; Department of Internal Medicine I, University Medical Center Schleswig-Holstein, Kiel, Germany., Tran F; Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel and University Medical Center Schleswig-Holstein, Kiel, Germany.; Department of Internal Medicine I, University Medical Center Schleswig-Holstein, Kiel, Germany., Lessing M; Department of Internal Medicine I, University Medical Center Schleswig-Holstein, Kiel, Germany., Bergfeld A; Department of Internal Medicine I, University Medical Center Schleswig-Holstein, Kiel, Germany., Hinz S; Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel and University Medical Center Schleswig-Holstein, Kiel, Germany.; Department of Internal Medicine I, University Medical Center Schleswig-Holstein, Kiel, Germany., Nikolaus S; Department of Internal Medicine I, University Medical Center Schleswig-Holstein, Kiel, Germany., Kümpers J; Department of Internal Medicine I, University Medical Center Schleswig-Holstein, Kiel, Germany., Matysiak A; Department of Internal Medicine I, University Medical Center Schleswig-Holstein, Kiel, Germany., Hofmann P; Institute of Immunology, Christian-Albrechts-University of Kiel and University Medical Center Schleswig-Holstein, Kiel, Germany.; Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel and University Medical Center Schleswig-Holstein, Kiel, Germany., Saggau C; Institute of Immunology, Christian-Albrechts-University of Kiel and University Medical Center Schleswig-Holstein, Kiel, Germany., Schneiders S; Institute of Immunology, Christian-Albrechts-University of Kiel and University Medical Center Schleswig-Holstein, Kiel, Germany.; Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel and University Medical Center Schleswig-Holstein, Kiel, Germany., Kamps AK; Institute of Immunology, Christian-Albrechts-University of Kiel and University Medical Center Schleswig-Holstein, Kiel, Germany.; Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel and University Medical Center Schleswig-Holstein, Kiel, Germany., Jacobs G; Institute of Epidemiology, Christian-Albrechts-University of Kiel and popgen Biobank, University Medical Center Schleswig-Holstein, Kiel, Germany., Lieb W; Institute of Epidemiology, Christian-Albrechts-University of Kiel and popgen Biobank, University Medical Center Schleswig-Holstein, Kiel, Germany., Maul J; Gastroenterologie am Bayerischen Platz, Berlin, Germany.; Department of Gastroenterology, Rheumatology and Infectious Diseases, Charité-Universitätsmedizin Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany., Siegmund B; Department of Gastroenterology, Rheumatology and Infectious Diseases, Charité-Universitätsmedizin Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany., Seegers B; Gastroenterology-Hepatology Center Kiel, Kiel, Germany., Hinrichsen H; Gastroenterology-Hepatology Center Kiel, Kiel, Germany., Oberg HH; Institute of Immunology, Christian-Albrechts-University of Kiel and University Medical Center Schleswig-Holstein, Kiel, Germany., Wesch D; Institute of Immunology, Christian-Albrechts-University of Kiel and University Medical Center Schleswig-Holstein, Kiel, Germany., Bereswill S; Institute of Microbiology, Infectious Diseases and Immunology, Charité-Universitätsmedizin Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany., Heimesaat MM; Institute of Microbiology, Infectious Diseases and Immunology, Charité-Universitätsmedizin Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany., Rupp J; Department of Infectious Diseases and Microbiology, University of Lübeck, Lübeck, Germany., Kniemeyer O; Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology-Hans Knoell Institute, Jena, Germany., Brakhage AA; Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology-Hans Knoell Institute, Jena, Germany.; Friedrich Schiller Universität, Jena, Germany., Brunke S; Institute of Microbiology, Department of Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product Research and Infection Biology-Hans Knoell Institute, Jena, Germany., Hube B; Friedrich Schiller Universität, Jena, Germany.; Institute of Microbiology, Department of Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product Research and Infection Biology-Hans Knoell Institute, Jena, Germany., Aden K; Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel and University Medical Center Schleswig-Holstein, Kiel, Germany.; Department of Internal Medicine I, University Medical Center Schleswig-Holstein, Kiel, Germany., Franke A; Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel and University Medical Center Schleswig-Holstein, Kiel, Germany., Iliev ID; The Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, Cornell University, New York, NY, USA.; Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medicine, Cornell University, New York, NY, USA.; Department of Microbiology and Immunology, Weill Cornell Medicine, Cornell University, New York, NY, USA., Scheffold A; Institute of Immunology, Christian-Albrechts-University of Kiel and University Medical Center Schleswig-Holstein, Kiel, Germany., Schreiber S; Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel and University Medical Center Schleswig-Holstein, Kiel, Germany.; Department of Internal Medicine I, University Medical Center Schleswig-Holstein, Kiel, Germany., Bacher P; Institute of Immunology, Christian-Albrechts-University of Kiel and University Medical Center Schleswig-Holstein, Kiel, Germany. p.bacher@ikmb.uni-kiel.de.; Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel and University Medical Center Schleswig-Holstein, Kiel, Germany. p.bacher@ikmb.uni-kiel.de.
Jazyk: angličtina
Zdroj: Nature medicine [Nat Med] 2023 Oct; Vol. 29 (10), pp. 2602-2614. Date of Electronic Publication: 2023 Sep 25.
DOI: 10.1038/s41591-023-02556-5
Abstrakt: Aberrant CD4 + T cell reactivity against intestinal microorganisms is considered to drive mucosal inflammation in inflammatory bowel diseases. The disease-relevant microbial species and the corresponding microorganism-specific, pathogenic T cell phenotypes remain largely unknown. In the present study, we identified common gut commensal and food-derived yeasts, as direct activators of altered CD4 + T cell reactions in patients with Crohn's disease (CD). Yeast-responsive CD4 + T cells in CD display a cytotoxic T helper cell (T H 1 cell) phenotype and show selective expansion of T cell clones that are highly cross-reactive to several commensal, as well as food-derived, fungal species. This indicates cross-reactive T cell selection by repeated encounter with conserved fungal antigens in the context of chronic intestinal disease. Our results highlighted a role of yeasts as drivers of aberrant CD4 + T cell reactivity in patients with CD and suggest that both gut-resident fungal commensals and daily dietary intake of yeasts might contribute to chronic activation of inflammatory CD4 + T cell responses in patients with CD.
(© 2023. The Author(s).)
Databáze: MEDLINE
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