Human pregnancy up-regulates Tim-3 in innate immune cells for systemic immunity.
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.
Zhao
Jie
J
Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Wuhan, The People's Republic of China.
Lei
Zhang
Z
Liu
Yanyan
Y
Li
Bo
B
Zhang
Liang
L
Fang
Haoshu
H
Song
Chuanwang
C
Wang
Xiaomei
X
Zhang
Gui-Mei
GM
Feng
Zuo-Hua
ZH
Huang
Bo
B
D000022:Abortion, Spontaneous / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D000072597:Hepatitis A Virus Cellular Receptor 2; D006801:Humans; D007113:Immunity, Innate; D015847:Interleukin-4 / Q000276:immunology / Q000378:metabolism; D008565:Membrane Proteins / Q000276:immunology / Q000378:metabolism*; D009000:Monocytes / Q000276:immunology*; D020411:Oligonucleotide Array Sequence Analysis; D011247:Pregnancy / Q000276:immunology*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050800:STAT6 Transcription Factor / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D015854:Up-Regulation
C448908:HAVCR2 protein, human; D000072597:Hepatitis A Virus Cellular Receptor 2; D008565:Membrane Proteins; D012333:RNA, Messenger; D050800:STAT6 Transcription Factor; D015847:Interleukin-4