IL-27 confers a protumorigenic activity of regulatory T cells via CD39.

ABSTRACT: Expression of ectonucleotidase CD39 contributes to the suppressive activity of Foxp3⁺ regulatory T cells (Tregs) by hydrolyzing immunogenic ATP into AMP. The molecular mechanism that drives CD39 expression on Tregs remains elusive. We found that tumor-infiltrating Tregs (Ti-Tregs) failed to up-regulate CD39 in mice lacking EBI3 subunit of IL-27 or IL-27Ra. Mixed bone marrow chimera and in vitro studies showed that IL-27 signaling in Tregs directly drives CD39 expression on Ti-Tregs in a STAT1-dependent, but STAT3- and T-bet-independent, manner. Tregs stimulated with IL-27 showed enhanced suppressive activities against CD8⁺ T cell responses in vitro. Moreover, IL-27Ra-deficient Tregs and STAT1-deficient Tregs were less efficient than WT Tregs in suppressing antitumor i

SUBMITTER: Park YJ 

PROVIDER: S-EPMC6386675 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature