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Human Pregnancy Up-Regulates Tim-3 in Innate Immune Cells for Systemic Immunity¹

Jie Zhao^*, Zhang Lei, Yanyan Liu, Bo Li, Liang Zhang, Haoshu Fang, Chuanwang Song, Xiaomei Wang, Gui-Mei Zhang, Zuo-Hua Feng and Bo Huang^2,

^* Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College; and Department of Biochemistry and Molecular Biology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, The People’s Republic of China

Pregnant women have both the local immune tolerance at the maternal-fetal interface and the systemic immune defense against pathogens. To date, regardless of the extensive investigation on the maternal-fetal immune tolerance, the maintenance of systemic immune defense in pregnant women still remains poorly understood. In the present study, we demonstrate that the immunoregulatory molecule T cell Ig and mucin domain (Tim)-3 plays important roles in innate and adaptive immunity of human pregnancy. During pregnancy, Tim-3 is strikingly up-regulated in peripheral blood of pregnant women, most by monocytes but not by T or B cells. The increased IL-4/STAT6 signaling may contribute to such up-regulation of Tim-3. In turn, the increased Tim-3 enhances not only innate immunity but also Th1-associated immune responses of pregnant women against pathogens. In contrast, our clinical data show that abnormal Tim-3 expression level might be connected to the pregnancy loss. In conclusion, our data show in this study that an immune regulatory molecule Tim-3, by virtue of its up-regulation in innate immune cells in pregnant women, enhances both innate and adaptive immune responses. Nevertheless, the abnormality of Tim-3 in pregnant woman may be deleterious to normal pregnancy.

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 work was supported by the National Natural Science Foundation of China (30871020, 30830095).

² Address correspondence and reprint requests to Dr. Bo Huang, Department of Biochemistry and Molecular Biology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, The People’s Republic of China. E-mail address: tjhuangbo{at}hotmail.com

³ Abbreviations used in this paper: hCG, human chorionic gonadotrophin; Tim, T cell Ig and mucin domain; DCFH-DA, 2',7'-dichlorfluorescein diacetate; CHIP, chromatin immunoprecipitation assay; iNOS, inducible NO synthase; TRIF, TIR-domain-containing adapter-inducing IFN-β.