IL-27 confers a protumorigenic activity of regulatory T cells via CD39.
basic_science · Level V
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- Record sourced from PubMed, PMID 30718407.
- Also identified by DOI 10.1073/pnas.1810254116 and PMC identifier 6386675.
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Abstract
Expression of ectonucleotidase CD39 contributes to the suppressive activity of Foxp3<sup>+</sup> 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<sup>+</sup> 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.
Medical subject headings
- Antigens, CD
- Apyrase
- Carcinogenesis
- Forkhead Transcription Factors
- STAT1 Transcription Factor