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

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,...

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Published inNature medicine Vol. 29; no. 10; p. 2602
Main Authors 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, Bereswill, Stefan, Heimesaat, Markus M, Rupp, Jan, Kniemeyer, Olaf, Brakhage, Axel A, Brunke, Sascha, Hube, Bernhard, Aden, Konrad, Franke, Andre, Iliev, Iliyan D, Scheffold, Alexander, Schreiber, Stefan, Bacher, Petra
Format Journal Article
LanguageEnglish
Published United States 01.10.2023
Subjects
CD4-Positive T-Lymphocytes
Clone Cells - pathology
Crohn Disease - microbiology
Humans
Inflammatory Bowel Diseases - pathology
Intestinal Mucosa - pathology
T-Lymphocytes, Helper-Inducer
Th1 Cells - pathology
Th17 Cells - pathology
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Summary: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 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.
ISSN:1546-170X