title: PSG9 Stimulates Increase in FoxP3+ Regulatory T-Cells through the TGF-β1 Pathway.
abstract: The pregnancy-specific glycoproteins (PSGs) are a family of proteins secreted by the syncytiotrophoblast of the placenta and are the most abundant trophoblastic proteins in maternal blood during the third trimester. The human PSG family consists of 10 protein-coding genes, some of which have a possible role in maintaining maternal immune tolerance to the fetus. PSG9 was reported as a potential predictive biomarker of pre-eclampsia, a serious complication of pregnancy that has been related to immunological dysfunction at the fetal-maternal interface. Therefore, we hypothesized that PSG9 may have an immunoregulatory role during pregnancy. We found that PSG9 binds to LAP and activates the latent form of TGF-β1. In addition, PSG9 induces the secretion of TGF-β1 from macrophages but not from CD4+ T-cells. TGF-β1 is required for the ex vivo differentiation of regulatory T-cells and, consistent with the ability of PSG9 to activate this cytokine, we observed that PSG9 induces the differentiation of FoxP3+ regulatory T-cells from naïve murine and human T-cells. Cytokines that are associated with inflammatory responses were also reduced in the supernatants of T-cells treated with PSG9, suggesting that PSG9, through its activation of TGFβ-1, could be a potent inducer of immune tolerance.
authors.affiliation: National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, United States of America.
authors.forename: Karlie
authors.initials: K
authors.lastname: Jones
authors.affiliation: National Institute on Deafness and other Communication Disorders, NIH, Bethesda, Maryland, United States of America.
authors.forename: Angela
authors.initials: A
authors.lastname: Ballesteros
authors.affiliation: Department of Pathology, USUHS, Bethesda, Maryland, 20814, United States of America.
authors.forename: Margaret
authors.initials: M
authors.lastname: Mentink-Kane
authors.affiliation: Department of Pathology, USUHS, Bethesda, Maryland, 20814, United States of America.
authors.forename: James
authors.initials: J
authors.lastname: Warren
authors.affiliation: Department of Pathology, USUHS, Bethesda, Maryland, 20814, United States of America.
authors.forename: Shemona
authors.initials: S
authors.lastname: Rattila
authors.affiliation: National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, United States of America.
authors.forename: Harry
authors.initials: H
authors.lastname: Malech
authors.affiliation: National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, United States of America.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Kang
authors.affiliation: Department of Pathology, USUHS, Bethesda, Maryland, 20814, United States of America.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Dveksler
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D018925:Chemokines / Q000378:metabolism; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D006801:Humans; D007107:Immune System; D007249:Inflammation; D007700:Kinetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011247:Pregnancy; D011268:Pregnancy-Specific beta 1-Glycoproteins / Q000378:metabolism*; D020349:Surface Plasmon Resonance; D050378:T-Lymphocytes, Regulatory / Q000166:cytology*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: D018925:Chemokines; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D011268:Pregnancy-Specific beta 1-Glycoproteins; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1