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

Qinghong Wang, Huan Ning, Hui Peng, Lin Wei, Rong Hou, Daniel F. Hoft and Jianguo Liu ()
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Qinghong Wang: Saint Louis University
Huan Ning: Saint Louis University
Hui Peng: Saint Louis University
Lin Wei: Hebei Medical University
Rong Hou: Saint Louis University
Daniel F. Hoft: Saint Louis University
Jianguo Liu: Saint Louis University

Nature Communications, 2017, vol. 8, issue 1, 1-11

Abstract: Abstract 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.

Date: 2017
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DOI: 10.1038/s41467-017-00892-y

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