Analysis of colon-infiltrating γδ Tcells in chronic inflammatory bowel disease and in colitis-associated cancer.

Abstract

Inflammatory bowel disease (IBD) remains a global health problem with a significant percentage of patients progressing to chronic inflammation and colitis-associated cancer (CAC). Whether or not γδ Tcells contribute to initiation and maintenance of inflammation in IBD and in the development of CAC is not known. We have evaluated the frequency, phenotype, and functions of γδ Tcells among tissue-infiltrating lymphocytes in healthy donors and IBD and CAC patients. Results show that Vδ1 Tcells are the dominant γδ T-cell population in healthy tissue, whereas Vδ2 T significantly abound in chronic IBD. Vδ2 Tcells produce more IFN-γ, TNF-α, and IL-17 than Vδ1 Tcells in chronic inflamed IBD. In CAC patients no significant cytokine production was detected in tissue-resident Vδ1 Tcells, but Vδ2 Tcells produced remarkable amounts of IFN-γ and TNF-α; these data were confirmed by the analysis of an independent cohort of IBD transcriptomes. Moreover, transcriptomes of IBD patients revealed a clear-cut clusterization of genes related with the maintenance of the inflammatory status. In conclusion, our results demonstrating that Vδ2 Tcells have a proinflammatory profile in chronic IBD are suggestive of their participation in IBD and CAC pathogenesis.