Details

Autor(en) / Beteiligte

• Wang, Qinghong
• Ning, Huan
• Peng, Hui
• Wei, Lin
• Hou, Rong
• Hoft, Daniel F
• Liu, Jianguo

Titel

Tristetraprolin inhibits macrophage IL-27-induced activation of antitumour cytotoxic T cell responses

Ist Teil von

• Nature communications, 2017-10, Vol.8 (1), p.867-11, Article 867

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2017

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• IFN-γ-producing cytotoxic T lymphocytes are essential for host defense against viral infection and cancer. Here we show that the RNA-binding tristetraprolin, encoded by Zfp36, is needed for CD8 T-cell production of IFN-γ in vivo. When activated in vitro, however, IFN-γ production by naive wild type and tristetraprolin-deficient CD8 T-cells is comparable. IL-27 is overproduced by tristetraprolin-deficient macrophages and increased systemically in tristetraprolin-deficient mice. Tristetraprolin suppresses IL-27 production by promoting p28 mRNA degradation. Importantly, deletion of IL-27 receptor WSX-1 in tristetraprolin-deficient mice (WSX-1/tristetraprolin double knockout) leads to a reduction in cytotoxic T lymphocyte numbers. Moreover, tumor growth is accelerated, not only in tristetraprolin-deficient mice after cytotoxic T lymphocyte depletion, but also in WSX-1/tristetraprolin double knockout mice, with substantial reduction in the number of tumor cytotoxic T lymphocytes. This study describes a regulatory pathway for IL-27 expression and cytotoxic T lymphocyte function mediated by tristetraprolin, contributing to regulation of antitumour immunity.IL-27 is one of a number of cytokines that can induce antitumour CD8 T cell responses. Here the authors show that TTP, encoded by Zfp36, degrades p28 to inhibit IL-27 production by macrophages and is thereby a negative regulator of the antitumour response.