| Autor: |
Quandt, Jasmin, Arnovitz, Stephen, Haghi, Leila, Woehlk, Janine, Mohsin, Azam, Okoreeh, Michael, Mathur, Priya S., Emmanuel, Akinola Olumide, Osman, Abu, Krishnan, Manisha, Morin, Samuel B., Pearson, Alexander T., Sweis, Randy F., Pekow, Joel, Weber, Christopher R., Khazaie, Khashayarsha, Gounari, Fotini |
| Zdroj: |
Nature Immunology; 20210101, Issue: Preprints p1-14, 14p |
| Abstrakt: |
The diversity of regulatory T (Treg) cells in health and in disease remains unclear. Individuals with colorectal cancer harbor a subpopulation of RORγt+Tregcells with elevated expression of β-catenin and pro-inflammatory properties. Here we show progressive expansion of RORγt+Tregcells in individuals with inflammatory bowel disease during inflammation and early dysplasia. Activating Wnt–β-catenin signaling in human and murine Tregcells was sufficient to recapitulate the disease-associated increase in the frequency of RORγt+Tregcells 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-inflammatory pathway genes. Sustained Wnt–β-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 Tregcells. Activation of β-catenin signaling interferes with this function and promotes the disease-associated RORγt+Tregphenotype. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
|
Full text from SpringerLink