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

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  • Additional Information
    • Source:
      Publisher: National Academy of Sciences Country of Publication: United States NLM ID: 7505876 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1091-6490 (Electronic) Linking ISSN: 00278424 NLM ISO Abbreviation: Proc Natl Acad Sci U S A Subsets: MEDLINE
    • Publication Information:
      Original Publication: Washington, DC : National Academy of Sciences
    • Subject Terms:
      Antigens, CD/*genetics ; Apyrase/*genetics ; Carcinogenesis/*genetics ; Forkhead Transcription Factors/*genetics ; STAT1 Transcription Factor/*genetics; Animals ; Gene Expression Regulation, Neoplastic ; Humans ; Interleukin-27/genetics ; Mice ; T-Lymphocytes, Regulatory/immunology ; T-Lymphocytes, Regulatory/metabolism ; Th17 Cells
    • 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.
      Competing Interests: The authors declare no conflict of interest.
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    • Contributed Indexing:
      Keywords: CD39; IL-27; STAT1; regulatory T cell; tumor immunity
    • Accession Number:
      0 (Antigens, CD)
      0 (FOXP3 protein, human)
      0 (Forkhead Transcription Factors)
      0 (Interleukin-27)
      0 (STAT1 Transcription Factor)
      EC 3.6.1.5 (Apyrase)
      EC 3.6.1.5 (CD39 antigen)
    • Publication Date:
      Date Created: 20190206 Date Completed: 20190503 Latest Revision: 20200309
    • Publication Date:
      20240829
    • Accession Number:
      PMC6386675
    • Accession Number:
      10.1073/pnas.1810254116
    • Accession Number:
      30718407