Upregulation of the Tim-3/Gal-9 pathway and correlation with the development of preeclampsia.
OBJECTIVE
It is well documented that an imbalance in immune tolerance at the maternal-fetal interface is likely to play an essential role in the etiology of preeclampsia. However, the mechanisms underlying immune tolerance during preeclampsia are still poorly understood. Tim-3, a Th1-specific cell surface molecule, is a relatively newly described molecule with important immunological functions. It can regulate Th1 responses with its ligand galectin-9 (Gal-9), and has become an attractive candidate for exploring the pathogenesis of preeclampsia.


METHODS
Twenty normal pregnancies and 20 preeclamptic pregnancies were enrolled in the present study. We examined the expression and function of Tim-3/Gal-9 in decidual tissue at the RNA and protein levels. In order to analyze their correlation with the development of preeclampsia, we measured the expression of Tim-3 on peripheral blood leukocytes using flow cytometry. IFN-γ, IL-10, and IL-17 in the peripheral blood plasma were measured by ELISA.


RESULTS
Tim-3/Gal-9 was upregulated in decidual tissue of preeclamptic vs. normotensive pregnancies. There was a significantly increased Th1 and Th17 response in PE as demonstrated by the upregulated levels of IFN-γ/IL-17, whereas IL-10 secreted by Th2 cells was sharply reduced.


CONCLUSIONS
The present study showed that an abnormal Tim-3/Gal-9 pathway was able to facilitate the development of preeclampsia. Our data uncovered a novel mechanism by which the Tim-3/Gal-9 pathway regulates immune responses, and we now identify this pathway as a potential therapeutic target in preeclampsia.
Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China; People's Hospital of Dancheng County, Zhoukou, Henan, PR China.
Haiyan
H
Hao
Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China.
Mengzhou
M
He
Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China; Faculty of Reproductive Medical Center of the Third Hospital Affiliated to Zhengzhou University, Zhengzhou, Henan, PR China.
Jing
J
Li
Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China.
Yuan
Y
Zhou
Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China.
Jing
J
Dang
Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China.
Fanfan
F
Li
Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China.
Meitao
M
Yang
Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China. Electronic address: dr.deng@tjh.tjmu.edu.cn.
Dongrui
D
Deng
D005260:Female; D037161:Galectins / Q000097:blood / Q000502:physiology*; D000072597:Hepatitis A Virus Cellular Receptor 2; D006801:Humans; D008565:Membrane Proteins / Q000097:blood / Q000502:physiology*; D011225:Pre-Eclampsia / Q000209:etiology* / Q000276:immunology; D011247:Pregnancy; D018417:Th1 Cells / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology; D015854:Up-Regulation
D037161:Galectins; C448908:HAVCR2 protein, human; D000072597:Hepatitis A Virus Cellular Receptor 2; C105032:LGALS9 protein, human; D008565:Membrane Proteins
Gal-9; Immune regulation; Preeclampsia; T help cells; Tim-3