Protection against inflammation- and autoantibody-caused fetal loss by the chemokine decoy receptor D6.
Fetal loss in animals and humans is frequently associated with inflammatory conditions. D6 is a promiscuous chemokine receptor with decoy function, expressed in lymphatic endothelium, that recognizes and targets to degradation most inflammatory CC chemokines. Here, we report that D6 is expressed in placenta on invading extravillous trophoblasts and on the apical side of syncytiotrophoblast cells, at the very interface between maternal blood and fetus. Exposure of D6-/- pregnant mice to LPS or antiphospholipid autoantibodies results in higher levels of inflammatory CC chemokines and increased leukocyte infiltrate in placenta, causing an increased rate of fetal loss, which is prevented by blocking inflammatory chemokines. Thus, the promiscuous decoy receptor for inflammatory CC chemokines D6 plays a nonredundant role in the protection against fetal loss caused by systemic inflammation and antiphospholipid antibodies.
Martinez de la Torre
Yeny
Y
Istituto Clinico Humanitas, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rozzano, 20089 Milan, Italy.
Buracchi
Chiara
C
Borroni
Elena M
EM
Dupor
Jana
J
Bonecchi
Raffaella
R
Nebuloni
Manuela
M
Pasqualini
Fabio
F
Doni
Andrea
A
Lauri
Eleonora
E
Agostinis
Chiara
C
Bulla
Roberta
R
Cook
Donald N
DN
Haribabu
Bodduluri
B
Meroni
Pierluigi
P
Rukavina
Daniel
D
Vago
Luca
L
Tedesco
Francesco
F
Vecchi
Annunciata
A
Lira
Sergio A
SA
Locati
Massimo
M
Mantovani
Alberto
A
D000818:Animals; D017152:Antibodies, Antiphospholipid / Q000494:pharmacology*; D019742:Chemokines, CC / Q000032:analysis; D005260:Female; D005313:Fetal Death / Q000209:etiology*; D007249:Inflammation / Q000150:complications*; D007962:Leukocytes; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D010920:Placenta / Q000737:chemistry; D011247:Pregnancy; D054447:Receptors, CCR10; D019707:Receptors, Chemokine / Q000502:physiology*; D014327:Trophoblasts / Q000737:chemistry; D000097628:Chemokine Receptor D6
D017152:Antibodies, Antiphospholipid; D019742:Chemokines, CC; D008070:Lipopolysaccharides; D054447:Receptors, CCR10; D019707:Receptors, Chemokine; D000097628:Chemokine Receptor D6