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


METHODS
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.
Department of Molecular Medicine, University La Sapienza, Viale Regina Elena 324, Rome 00161 Italy.
Claudia
C
Carlino
Eleonora
E
Trotta
Helena
H
Stabile
Stefania
S
Morrone
Roberta
R
Bulla
Alessandra
A
Soriani
Maria Luisa
ML
Iannitto
Chiara
C
Agostinis
Carlo
C
Mocci
Massimo
M
Minozzi
Cesare
C
Aragona
Giorgia
G
Perniola
Francesco
F
Tedesco
Silvano
S
Sozzani
Angela
A
Santoni
Angela
A
Gismondi
D002196:Capillaries / Q000378:metabolism; D002465:Cell Movement / Q000276:immunology; D018925:Chemokines / Q000235:genetics / Q000378:metabolism*; D003656:Decidua / Q000098:blood supply / Q000166:cytology* / Q000502:physiology; D042783:Endothelial Cells / Q000166:cytology* / Q000502:physiology; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D007694:Killer Cells, Natural / Q000166:cytology*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D018919:Neovascularization, Physiologic / Q000502:physiology; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism; D017154:Stromal Cells / Q000166:cytology / Q000502:physiology; D014327:Trophoblasts / Q000166:cytology / Q000502:physiology
C102741:CMKLR1 protein, human; D018925:Chemokines; D036341:Intercellular Signaling Peptides and Proteins; C478630:RARRES2 protein, human; D012333:RNA, Messenger; D019707:Receptors, Chemokine