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* Department of Immunology and Medical Zoology, Hyogo College of Medicine, Hyogo, Japan;
Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Saitama, Japan;
Intractable Immune System Disease Research Center; and
Department of Immunology, Tokyo Medical University, Tokyo, Japan
IL-27 up-regulates Th1 but down-regulates Th2 responses. However, its molecular mechanism and regulatory effects on polarized Th2 cells remain unclear. In this study, we have revealed that IL-27 inhibits Th2 cell development as well as Th2 cytokines production from already polarized Th2 cells by down-regulation of GATA-3 and up-regulation of T-bet expression simultaneously. In vivo daily IL-27 treatment for 1 wk after Leishmania major infection protects BALB/c mice from footpad swelling by diminishing parasite burden via reciprocal regulation of Th1 and Th2 responses. Furthermore, IL-27 stimulation causes marked reduction in the capacity of host mouse to mount a Th2 response against Strongyloides venezuelensis infection. Thus, IL-27-treated mice failed to develop intestinal mastocytosis after S. venezuelensis infection and exhibited a marked delay in parasite expulsion. Finally, intranasal administration of IL-27 inhibits OVA-induced airway hyperresponsiveness and inflammation in OVA-sensitized animals. Thus, IL-27 could provide us with a novel therapeutic way for treating Th2-associated diseases such as bronchial asthma.
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 by a Grant-in-Aid for Scientific Research on Priority Areas and Hitech Research Center Grant from the Ministry of Education, Culture, Sports, Science, and Technology of Japan.
2 Address correspondence and reprint requests to Dr. Tomohiro Yoshimoto, Department of Immunology and Medical Zoology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, Japan. E-mail address: tomo{at}hyo-med.ac.jp
3 Abbreviations used in this paper: EBI3, EBV-induced gene 3; AHR, airway hyperresponsiveness; Tg, transgenic; L3, third-stage larvae; mMCP-1, mouse mast cell protease 1; Th-17, IL-17-porducing helper T.
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