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Selection of cross-reactive T cells by commensal and food-derived yeasts drives pathogenic cytotoxic Th1 responses in Crohn´s disease

ABSTRACT: Aberrant CD4+ T cell reactivity against intestinal microbes is considered to drive mucosal inflammation in inflammatory bowel diseases. The disease-relevant microbial species and the corresponding microbe-specific pathogenic T cell phenotypes remain unknown. Here, we identify common gut commensal and food-derived yeasts, as direct activators of aberrant CD4+ T cell reactions in patients with Crohn´s disease (CD). Yeast-responsive CD4+ T cells in CD display a cytotoxic Th1 phenotype and selective clonal expansion of cells 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 highlight a role of fungi in driving immunopathology in patients with CD and suggest that both, gut-resident fungal commensals, and daily dietary intake of yeasts, may contribute to chronic activation of pathogenic CD4+ T cell responses involved in disease pathophysiology.

ORGANISM(S): Homo sapiens

PROVIDER: GSE227638 | GEO | 2023/08/15

REPOSITORIES: GEO

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