| First Author | Quandt J | Year | 2021 |
| Journal | Nat Immunol | Volume | 22 |
| Issue | 4 | Pages | 471-484 |
| PubMed ID | 33664518 | Mgi Jnum | J:305306 |
| Mgi Id | MGI:6706383 | Doi | 10.1038/s41590-021-00889-2 |
| Citation | Quandt J, et al. (2021) Wnt-beta-catenin activation epigenetically reprograms Treg cells in inflammatory bowel disease and dysplastic progression. Nat Immunol 22(4):471-484 |
| abstractText | The diversity of regulatory T (Treg) cells in health and in disease remains unclear. Individuals with colorectal cancer harbor a subpopulation of RORgammat(+) Treg cells with elevated expression of beta-catenin and pro-inflammatory properties. Here we show progressive expansion of RORgammat(+) Treg cells in individuals with inflammatory bowel disease during inflammation and early dysplasia. Activating Wnt-beta-catenin signaling in human and murine Treg cells was sufficient to recapitulate the disease-associated increase in the frequency of RORgammat(+) Treg cells coexpressing multiple pro-inflammatory cytokines. Binding of the beta-catenin interacting partner, TCF-1, to DNA overlapped with Foxp3 binding at enhancer sites of pro-inflammatory pathway genes. Sustained Wnt-beta-catenin activation induced newly accessible chromatin sites in these genes and upregulated their expression. These findings indicate that TCF-1 and Foxp3 together limit the expression of pro-inflammatory genes in Treg cells. Activation of beta-catenin signaling interferes with this function and promotes the disease-associated RORgammat(+) Treg phenotype. |
