Wnt-β-catenin activation epigenetically reprograms T_reg cells in inflammatory bowel disease and dysplastic progression.

ABSTRACT: The diversity of regulatory T (T_reg) cells in health and in disease remains unclear. Individuals with colorectal cancer harbor a subpopulation of RORγt⁺ T_reg cells with elevated expression of β-catenin and pro-inflammatory properties. Here we show progressive expansion of RORγt⁺ T_reg cells in individuals with inflammatory bowel disease during inflammation and early dysplasia. Activating Wnt-β-catenin signaling in human and murine T_reg cells was sufficient to recapitulate the disease-associated increase in the frequency of RORγt⁺ T_reg cells coexpressing multiple pro-inflammatory cytokines. Binding of the β-catenin interacting partner, TCF-1, to DNA overlapped with Foxp3 binding at enhancer sites of pro-i

SUBMITTER: Quandt J 

PROVIDER: S-EPMC8262575 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature