Role of commensal-specific γδ T-Cell Responses in Crohn’s Disease

Crohn’s disease (CD) has evolved into a global health challenge, underscoring the need for new therapeutic strategies. The pathogenesis of CD is complex and multifactorial, involving gut epithelial barrier defects, dysregulated immune responses, and a dysbiotic microbiota. Prior studies show that Bifidobacterium longum, a common gut commensal, is depleted in CD patients, but its mechanisms in intestinal immune system regulation are still unclear. We have found that Bifidobacterium longum antigens can be recognized by T cell receptors expressed on T cells. We hypothesized that the loss of Bifidobacterium longum may lead to a loss of T cells in the gut of CD patients. Using flow cytometry, we analyzed T cell prevalence in inflamed and paired non-inflamed colonic tissues of CD patients. We found a significant reduction in T cells within UC-affected tissue, suggesting impaired T cellmediated immune regulation. We also found that T cells from the noninflamed CD colon can be activated in response to Bifidobacterium longum antigens, indicating a potential role in gut homeostasis. These results highlight the need to further investigate how microbial antigens shape T cell function, which may provide insights into novel therapeutic strategies for CD.