IL-27 confers a protumorigenic activity of regulatory T cells via CD39
- 주제(키워드) regulatory T cell , tumor immunity , CD39 , IL-27 , STAT1
- 주제(기타) Multidisciplinary Sciences
- 설명문(일반) [Park, Young-Jun; Ryu, Heeju; Choi, Garam; Kim, Byung-Seok; Chung, Yeonseok] Seoul Natl Univ, Pharmaceut Sci Res Inst, Lab Immune Regulat, Seoul 151742, South Korea; [Park, Young-Jun; Ryu, Heeju; Choi, Garam; Chung, Yeonseok] Seoul Natl Univ, Coll Pharm, BK21 Plus Program, Seoul 151742, South Korea; [Hwang, Eun Sook] Ewha Womans Univ, Coll Pharm, Seoul 03760, South Korea; [Hwang, Eun Sook] Ewha Womans Univ, Grad Sch Pharmaceut Sci, Seoul 03760, South Korea; [Kim, Hun Sik] Univ Ulsan, Coll Med, Asan Inst Life Sci, Dept Biomed Sci,Asan Med Ctr, Seoul 05505, South Korea
- 등재 SCIE, SCOPUS
- OA유형 Bronze, Green Published
- 발행기관 NATL ACAD SCIENCES
- 발행년도 2019
- URI http://www.dcollection.net/handler/ewha/000000160030
- 본문언어 영어
- Published As http://dx.doi.org/10.1073/pnas.1810254116
- PubMed https://pubmed.ncbi.nlm.nih.gov/30718407
초록/요약
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.
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