title: Endogenous TWEAK is critical for regulating the function of mouse uterine natural killer cells in an immunological model of pregnancy loss.
abstract: Uterine natural killer (uNK) cells are the most abundant lymphocyte population in the feto-maternal interface during early gestation, and uNK cells play a significant role in the establishment and maintenance of pregnancy-related vascularization, as well as in tolerance to the fetus. Tumour necrosis factor-like weak inducer of apoptosis (TWEAK) and its receptor, fibroblast growth factor-inducible molecule (Fn14), are involved in preventing local cytotoxicity and counterbalancing the cytotoxic function of uNK cells. Here, we studied the regulation of TWEAK/Fn14-mediated innate immunity in the uterus using a lipopolysaccharide (LPS)-induced model of abortion in pregnant mice. Specifically, we detected the expression of TWEAK and Fn14 in the uterus and in uNK cells following LPS treatment. Our results revealed that TWEAK and Fn14 are expressed by uNK cells in pregnant mice; in particular, it appears that the cytokine TWEAK is primarily derived from uNK cells. Interestingly, the down-regulation of TWEAK in uNK cells and the up-regulation of the Fn14 receptor in the uterus in LPS-treated mice may contribute to the disruption of decidual homeostasis by altering uNK cell cytotoxicity - ultimately leading to fetal rejection. In conclusion, the present study strongly suggests that the TWEAK-Fn14 axis in uNK cells is involved in maintaining the tolerance necessary for successful pregnancy.
authors.affiliation: College of Veterinary Medicine of Northwest A&F University, Shaanxi, China.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Qi
authors.affiliation: College of Veterinary Medicine of Northwest A&F University, Shaanxi, China.
authors.forename: Mingzhu
authors.initials: M
authors.lastname: Lei
authors.affiliation: College of Veterinary Medicine of Northwest A&F University, Shaanxi, China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Qin
authors.affiliation: College of Veterinary Medicine of Northwest A&F University, Shaanxi, China.
authors.forename: Mengjie
authors.initials: M
authors.lastname: Xie
authors.affiliation: College of Veterinary Medicine of Northwest A&F University, Shaanxi, China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Zhao
authors.affiliation: College of Veterinary Medicine of Northwest A&F University, Shaanxi, China.
authors.forename: Jingyu
authors.initials: J
authors.lastname: Wang
mesh_terms: D000022:Abortion, Spontaneous / Q000209:etiology* / Q000276:immunology; D000818:Animals; D000074049:Cytokine TWEAK; D004195:Disease Models, Animal; D005260:Female; D007694:Killer Cells, Natural / Q000276:immunology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000032:analysis; D011247:Pregnancy; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology; D000074050:TWEAK Receptor; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D048069:Tumor Necrosis Factors / Q000502:physiology*; D014599:Uterus / Q000276:immunology*
chemical_list: D000074049:Cytokine TWEAK; D008070:Lipopolysaccharides; D055655:NK Cell Lectin-Like Receptor Subfamily K; D018124:Receptors, Tumor Necrosis Factor; D000074050:TWEAK Receptor; C000613299:Tnfrsf12a protein, mouse; C491645:Tnfsf12 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D048069:Tumor Necrosis Factors
keywords: fibroblast growth factor-inducible molecule; lipopolysaccharide-induced abortion; pregnant mice; tumour necrosis factor-like weak inducer of apoptosis; uterine natural killer cell cytotoxicity