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Augmentation of Antigen-Presenting and Th1-Promoting Functions of Dendritic Cells by WSX-1(IL-27R) Deficiency¹

Department of Biomolecular Sciences, Faculty of Medicine, Saga University, Saga, Japan

WSX-1 is the subunit of the IL-27R complex expressed by T, B, NK/NKT cells, as well as macrophages and dendritic cells (DCs). Although it has been shown that IL-27 has both stimulatory and inhibitory effects on T cells, little is known on the role of IL-27/WSX-1 on DCs. LPS stimulation of splenic DCs in vivo resulted in prolonged CD80/CD86 expression on WSX-1-deficient DCs over wild-type DCs. Upon LPS stimulation in vitro, WSX-1-deficient DCs expressed Th1-promoting molecules higher than wild-type DCs. In an allogeneic MLR assay, WSX-1-deficient DCs were more potent than wild-type DCs in the induction of proliferation of and IFN- production by responder cell proliferation. When cocultured with purified NK cells, WSX-1-deficient DCs induced higher IFN- production and killing activity of NK cells than wild-type DCs. As such, Ag-pulsed WSX-1-deficient DCs induced Th1-biased strong immune responses over wild-type DCs when transferred in vivo. WSX-1-deficient DCs were hyperreactive to LPS stimulation as compared with wild-type DCs by cytokine production. IL-27 suppressed LPS-induced CD80/86 expression and cytokine production by DCs in vitro. Thus, our study demonstrated that IL-27/WSX-1 signaling potently down-regulates APC function and Th1-promoting function of DCs to modulate overall immune responses.

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, Sports and Culture (to H.Y.), Japan Society for the Promotion of Science (to H.Y.), Japan Research Foundation for Clinical Pharmacology (to H.Y.), Sumitomo Foundation, Basic Science Research Projects (to H.Y.), Naito Foundation (to H.Y.), and Takeda Science Foundation. This work was also supported by the president’s research project expenditure of Saga University (to H.Y.). W.S. is a recipient of the Japan Society for the Promotion of Science Postdoctoral Fellowship for foreign researchers.

² Address correspondence and reprint requests to Dr. Hiroki Yoshida, Department of Biomolecular Sciences, Faculty of Medicine, Saga University, Nabeshima, Saga, Japan. E-mail address: yoshidah{at}med.saga-u.ac.jp

³ Abbreviations used in this paper: DC, dendritic cell; BM, bone marrow; WT, wild type; KLH, keyhole limpet hemocyanin; LN, lymph node; MFI, mean fluorescence intensity; SOCS, suppressor of cytokine signaling; BM, bone marrow; KO, knockout.

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