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

## TL;DR

Crohn’s disease involves abnormal T cell responses to gut and dietary yeasts, leading to inflammation.

## Contribution

Identifies cross-reactive T cells activated by commensal and food yeasts as drivers of CD4+ TH1 responses in Crohn’s disease.

## Key findings

- Yeast-responsive CD4+ T cells in Crohn’s disease show a cytotoxic TH1 cell phenotype.
- T cell clones are selectively expanded and cross-reactive to multiple fungal species.
- Gut-resident and dietary yeasts contribute to chronic T cell activation in Crohn’s disease.

## Abstract

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 (TH1 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.

In patients with Crohn’s disease, CD4+ T cells with cytotoxic TH1 cell-like effector functions reactive against dietary and commensal yeasts are increased in blood and inflamed tissue compared with patients with ulcerative colitis and healthy controls.