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,¶,¶
* Division of Molecular and Cellular Immunology, Medical Institute of Bioregulation and Department of
Ophthalmology and
Department of Parasitology, Graduate School of Medical Sciences; Kyushu University, Fukuoka, Japan;
Precursory Research for Embryonic Science and Technology, Japan Science and Technology Agency, Honcho Kawaguchi, Japan; and
¶ Department of Biomolecular Sciences, Faculty of Medicine, Saga University, Saga, Japan
Recent lines of evidence have demonstrated that IL-27, a newly identified IL-12-related cytokine, has two apparently conflicting roles in immune responses: one as an initiator of Th1 responses and the other as an attenuator of inflammatory cytokine production. Although the IL-27-mediated Th1 initiation mechanism has been elucidated, little is known about the molecular basis for the suppression of cytokine production. In the present study, we demonstrated that IL-27 suppressed the production of various proinflammatory cytokines by fully activated CD4+ T cells while it had no effect on the cytokine production by CD4+ T cells at early phases of activation. IL-27 also suppressed IL-17 production by activated CD4+ T cells, thereby counteracting IL-23, another IL-12-related cytokine with proinflammatory effects. In fully activated CD4+ T cells, STAT3 was preferentially activated by IL-27 stimulation, whereas both STAT1 and 3 were activated by IL-27 in early activated CD4+ T cells. Lack of STAT3 in fully activated cells impaired the suppressive effects of IL-27. These data indicated that the preferential activation of STAT3 in fully activated CD4+ T cells plays an important role in the cytokine suppression by IL-27/WSX-1.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This study was supported in part by grants from the Ministry of Education, Science, Technology, Sports and Culture of Japan (to H.Y. and A.Y.), from Terumo Life Science Foundation (to S.H.), from Japan Research Foundation for Clinical Pharmacology (to H.Y.), from the Sumitomo Foundation, Grant for Basic Science Research Projects (to H.Y.), and from the Naito Foundation (to H.Y.). This work was also supported by the president’s expenditure (research project expenditure) of Saga University (to H.Y.).
2 Address correspondence and reprint requests to Dr. Hiroki Yoshida, Department of Biomolecular Sciences, Faculty of Medicine, Saga University, Nabeshima, Saga, 849-8501, Japan. E-mail address: yoshidah{at}med.saga-u.ac.jp
3 Abbreviations used in this paper: SOCS, suppressor of cytokine signaling; LMNC, liver mononuclear cell; pY, anti-phosphotyrosine.
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