Chemerin regulates NK cell accumulation and endothelial cell morphogenesis in the decidua during early pregnancy

Claudia Carlino, Eleonora Trotta, Helena Stabile, Stefania Morrone, Roberta Bulla, Alessandra Soriani, Maria Luisa Iannitto, Chiara Agostinis, Carlo Mocci, Massimo Minozzi, Cesare Aragona, Giorgia Perniola, Francesco Tedesco, Silvano Sozzani, Angela Santoni, Angela Gismondi

Research output: Contribution to journalArticlepeer-review

Abstract

Context: Although decidual natural killer (NK) cell accumulation and vascular remodeling are critical steps to ensure successful pregnancy, the molecular mechanisms controlling these events are poorly defined. Objective: Herein we analyzed whether chemerin, a recently identified chemoattractant involved in many pathophysiological processes, could be expressed in the uterine compartment and could regulate events relevant for the good outcome of pregnancy. Design: Chemerin expression in human primary culture of stromal (ST) cells, extravillous trophoblast cells, and decidual endothelial cells (DEC) was analyzed by RT-PCR, ELISA, and Western blot. Migration through ST or DEC of peripheral blood and decidual (d) NK cells from pregnant women was performed using a transwell assay. A DEC capillary-like tube formation assay was used to evaluate endothelial morphogenesis. Results: Chemerin is differentially expressed by decidual cells during early pregnancy being present at high levels in ST and extravillous trophoblast cells but not in DEC. Notably, ST cells from pregnant women exhibit and release higher levels of chemerin as compared with ST cells from menopausal or fertile nonpregnant women. Chemerin can support peripheral blood NK cell migration through both DEC and ST cells. Although dNK cells exhibit lower chemerin receptor (CMKLR1) expression than their blood counterpart, CMKLR1 engagement on dNK cells resulted in both ERK activation and migration through decidual ST cells. Interestingly, DEC also express CMKLR1 and undergo ERK activation and capillary-like tube structure formation upon exposure to chemerin. Conclusions: Our data indicate that chemerin is up-regulated during decidualization and might contribute to NK cell accumulation and vascular remodeling during early pregnancy.

Original languageEnglish
Pages (from-to)3603-3612
Number of pages10
JournalJournal of Clinical Endocrinology and Metabolism
Volume97
Issue number10
DOIs
Publication statusPublished - Oct 2012

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Endocrinology
  • Biochemistry, medical
  • Endocrinology, Diabetes and Metabolism

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