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Martini, Gabriela Rios; Tikhonova, Ekaterina; Rosati, Elisa; DeCelie, Meghan Bialt; Sievers, Laura Katharina; Tran, Florian; Lessing, Matthias; Bergfeld, Arne; Hinz, Sophia; Nikolaus, Susanna; Kümpers, Julia; Matysiak, Anna; Hofmann, Philipp; Saggau, Carina; Schneiders, Stephan; Kamps, Ann-Kristin; Jacobs, Gunnar; Lieb, Wolfgang; Maul, Jochen; Siegmund, Britta; Seegers, Barbara; Hinrichsen, Holger; Oberg, Hans-Heinrich; Wesch, Daniela; [...]

Selection of cross-reactive T cells by commensal and food-derived yeasts drives cytotoxic TH1 cell responses in Crohn’s disease

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  • Media type: E-Article
  • Title: Selection of cross-reactive T cells by commensal and food-derived yeasts drives cytotoxic TH1 cell responses in Crohn’s disease
  • Contributor: Martini, Gabriela Rios; Tikhonova, Ekaterina; Rosati, Elisa; DeCelie, Meghan Bialt; Sievers, Laura Katharina; Tran, Florian; Lessing, Matthias; Bergfeld, Arne; Hinz, Sophia; Nikolaus, Susanna; Kümpers, Julia; Matysiak, Anna; Hofmann, Philipp; Saggau, Carina; Schneiders, Stephan; Kamps, Ann-Kristin; Jacobs, Gunnar; Lieb, Wolfgang; Maul, Jochen; Siegmund, Britta; Seegers, Barbara; Hinrichsen, Holger; Oberg, Hans-Heinrich; Wesch, Daniela; [...]
  • imprint: Springer Science and Business Media LLC, 2023
  • Published in: Nature Medicine
  • Language: English
  • DOI: 10.1038/s41591-023-02556-5
  • ISSN: 1078-8956; 1546-170X
  • Keywords: General Biochemistry, Genetics and Molecular Biology ; General Medicine
  • Origination:
  • Footnote:
  • Description: <jats:title>Abstract</jats:title><jats:p>Aberrant CD4<jats:sup>+</jats:sup> 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<jats:sup>+</jats:sup> T cell reactions in patients with Crohn’s disease (CD). Yeast-responsive CD4<jats:sup>+</jats:sup> T cells in CD display a cytotoxic T helper cell (T<jats:sub>H</jats:sub>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<jats:sup>+</jats:sup> 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<jats:sup>+</jats:sup> T cell responses in patients with CD.</jats:p>