title: Tim-3: Expression on immune cells and roles at the maternal-fetal interface.
abstract: Successful pregnancy relies on the accurate regulation of the maternal-fetal immune system. Without enough tolerance in the uterine microenvironment, the mother and the hemiallogeneic fetus could not peacefully coexist. T cell immunoglobulin and mucin domain (Tim)-3 is a molecule originally regarded as to be expressed on terminally differentiated IFN-γ expressing CD4+T cells (Th1). The engagement of Tim-3 with its ligand, galectin-9 (Gal-9) could induce the exhaustion or apoptosis of effector T cells, and thus might regulate the tolerance. Tim-3 pathway also participates in regulating the activities of CD4+regulatory T cells, monocyte-macrophages, dendritic cells and natural killer cells. Dysregulation of Tim-3 expression can elicit excessive or inhibited inflammatory responses and ultimately result in autoimmune diseases, viral or tumor evasion and pregnancy complications. In this review, we will mainly focus on the expression of Tim-3 on local immune cells and its function in pregnancy. In addition, meaningful questions that need further investigation and the potential roles of Tim-3 in fetal tolerance will be discussed. Deeper understanding of the immune checkpoint receptor Tim-3 will shed new light on exploring the pathogenesis of some pregnancy complications, including pre-eclampsia, intrauterine growth restriction, recurrent spontaneous abortion and preterm birth. Tim-3 pathway might be a new target of immune therapy for pregnancy complications in the future.
authors: Family Planning Research Institute, Center for Reproductive Medicine, Tongji Medical College, Huazhong University of Science and Technology, 430030 Wuhan, PR China.
authors: Xiao-Hui
authors: XH
authors: Hu
authors: Department for Reproductive Medicine, Ghent University Hospital, De Pintelaan 185, Ghent 9000, Belgium.
authors: Mao-Xing
authors: MX
authors: Tang
authors: Department of Obstetrics, Gynecology & Reproductive Sciences, Reproductive Immunology Unit, Yale University School of Medicine, 333 Cedar St. LSOG 305A, New Haven, CT 06520, USA. Electronic address: gil.mor@yale.edu.
authors: Gil
authors: G
authors: Mor
authors: Family Planning Research Institute, Center for Reproductive Medicine, Tongji Medical College, Huazhong University of Science and Technology, 430030 Wuhan, PR China. Electronic address: aihua_liao@sina.com.
authors: Ai-Hua
authors: AH
authors: Liao
mesh_terms: D000026:Abortion, Habitual / Q000276:immunology*; D000818:Animals; D005260:Female; D047109:Fetal Development; D037161:Galectins / Q000378:metabolism; D005786:Gene Expression Regulation; D000072597:Hepatitis A Virus Cellular Receptor 2 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007108:Immune Tolerance; D007694:Killer Cells, Natural / Q000276:immunology*; D008431:Maternal-Fetal Exchange / Q000276:immunology; D011225:Pre-Eclampsia / Q000276:immunology*; D011247:Pregnancy; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D037161:Galectins; C448908:HAVCR2 protein, human; D000072597:Hepatitis A Virus Cellular Receptor 2; C105032:LGALS9 protein, human
keywords: Immunoregulation; Maternal-fetal interface; Pregnancy; Tim-3