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IL-27 confers a protumorigenic activity of regulatory T cells via CD39
- Title
- IL-27 confers a protumorigenic activity of regulatory T cells via CD39
- Authors
- Park, Young-Jun; Ryu, Heeju; Choi, Garam; Kim, Byung-Seok; Hwang, Eun Sook; Kim, Hun Sik; Chung, Yeonseok
- Ewha Authors
- 황은숙
- SCOPUS Author ID
- 황은숙
- Issue Date
- 2019
- Journal Title
- PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
- ISSN
- 0027-8424
- Citation
- PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA vol. 116, no. 8, pp. 3106 - 3111
- Keywords
- regulatory T cell; tumor immunity; CD39; IL-27; STAT1
- Publisher
- NATL ACAD SCIENCES
- Indexed
- SCIE; SCOPUS
- Document Type
- Article
- 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.
- DOI
- 10.1073/pnas.1810254116
- Appears in Collections:
- 약학대학 > 약학과 > Journal papers
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