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

Young Jun Park, Heeju Ryu, Garam Choi, Byung Seok Kim, Eun Sook Hwang, Hun Sik Kim, Yeonseok Chung

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

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 immunity in vivo. CD39 inhibition significantly abolished IL-27–induced suppressive activities of Tregs. Thus, IL-27 signaling in Tregs critically contributes to protumorigenic properties of Tregs via up-regulation of CD39.

Original languageEnglish
Pages (from-to)3106-3111
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume116
Issue number8
DOIs
StatePublished - 19 Feb 2019

Keywords

  • CD39
  • IL-27
  • Regulatory T cell
  • STAT1
  • Tumor immunity

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