Placental Protein 13 (PP13) – A Placental Immunoregulatory Galectin Protecting Pregnancy

Abstract

Galectins are glycan-binding proteins that regulate innate and adaptive immune responses, and some confer maternal-fetal immune tolerance in eutherian mammals. A chromosome 19 cluster of galectins has emerged in anthropoid primates, species with deep placentation and long gestation. Three of the five human cluster galectins are solely expressed in the placenta, where they may confer additional immunoregulatory functions to enable deep placentation. One of these is galectin-13, also known as Placental Protein 13 (PP13). It has a “jelly-roll” fold, carbohydrate-recognition domain and sugar-binding preference resembling other mammalian galectins. PP13 is predominantly expressed by the syncytiotrophoblast and released from the placenta into the maternal circulation. Its ability to induce apoptosis of activated T cells in vitro, and to divert and kill T cells as well as macrophages in the maternal decidua in situ, suggests important immune functions. Indeed, mutations in the promoter and an exon of LGALS13 presumably leading to altered or non-functional protein expression are associated with a higher frequency of preeclampsia and other obstetrical syndromes, which involve immune dysregulation. Moreover, decreased placental expression of PP13 and its low concentrations in first trimester maternal sera are associated with elevated risk of preeclampsia. Indeed, PP13 turned to be a good early biomarker to assess maternal risk for the subsequent development of pregnancy complications caused by impaired placentation. Due to the ischemic placental stress in preterm preeclampsia, there is increased trophoblastic shedding of PP13 immunopositive microvesicles starting in the second trimester, which leads to high maternal blood PP13 concentrations. Our meta-analysis suggests that this phenomenon may enable the potential use of PP13 in directing patient management near to or at the time of delivery. Recent findings on the beneficial effects of PP13 on decreasing blood pressure due to vasodilatation in pregnant animals suggest its therapeutic potential in preeclampsia.

Comparison of syncytiotrophoblast generated from human embryonic stem cells and from term placentas

“…The concentration of at least one of these antigens (LGALS13) rises in maternal serum as pregnancy progresses (29,30). Transcripts for seven members of this large gene family were detectable in ESCd >70 and PHTd cells (SI Appendix, Fig.…”

Placenta-derived exosomes: potential biomarkers of preeclampsia

“…72 Studies involving PP13 as a biomarker are limited, due to the lack of sample-population homogeneity and poor detection sensitivity; in addition, sensitivity and specificity for detection has to be determined using predefined cutoff values. Interestingly, STBEVs have been shown to be immunopositive for PP13, 70 suggestive of an immunomodulatory role. Therefore, future studies must evaluate PP13-biomarker potential in association with STBEVs and exosomes.…”

“…Placental protein PP13 has been reported extensively in early placental development, 69,70 and may be involved in T-cell and macrophage apoptosis, regulation of maternal immunoresponses, and maternal-fetal immunomodulation. 70,71 Due to its association with early placental development, it may be useful in detecting PE during early pregnancy.…”

“…70,71 Due to its association with early placental development, it may be useful in detecting PE during early pregnancy. 72 A significantly lower concentration of PP13 in weeks 6-10 of gestation has been found in PE-predisposed patients, which was attributed to impaired trophoblastic regulation and spiral-artery remodeling in PE.…”

Carbohydrate Recognition Mechanism of the Mushroom Galectin ACG

“…Interestingly, this protein is strongly associated with placental immunity, and is named PP13. Recent studies support the idea that PP13 is a placental immunoregulatory protein that protects pregnancy (50).…”