期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 116, 期 8, 页码 3106-3111出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1810254116
关键词
regulatory T cell; tumor immunity; CD39; IL-27; STAT1
资金
- National Research Foundation of Korea [2017R1A2B3007392, 0430-20150023]
- National Research Foundation of Korea [2017R1A2B3007392] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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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