title: Protection against inflammation- and autoantibody-caused fetal loss by the chemokine decoy receptor D6.
abstract: 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.
authors.affiliation: Istituto Clinico Humanitas, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rozzano, 20089 Milan, Italy.
authors.forename: Yeny
authors.initials: Y
authors.lastname: Martinez de la Torre
authors.forename: Chiara
authors.initials: C
authors.lastname: Buracchi
authors.forename: Elena M
authors.initials: EM
authors.lastname: Borroni
authors.forename: Jana
authors.initials: J
authors.lastname: Dupor
authors.forename: Raffaella
authors.initials: R
authors.lastname: Bonecchi
authors.forename: Manuela
authors.initials: M
authors.lastname: Nebuloni
authors.forename: Fabio
authors.initials: F
authors.lastname: Pasqualini
authors.forename: Andrea
authors.initials: A
authors.lastname: Doni
authors.forename: Eleonora
authors.initials: E
authors.lastname: Lauri
authors.forename: Chiara
authors.initials: C
authors.lastname: Agostinis
authors.forename: Roberta
authors.initials: R
authors.lastname: Bulla
authors.forename: Donald N
authors.initials: DN
authors.lastname: Cook
authors.forename: Bodduluri
authors.initials: B
authors.lastname: Haribabu
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Meroni
authors.forename: Daniel
authors.initials: D
authors.lastname: Rukavina
authors.forename: Luca
authors.initials: L
authors.lastname: Vago
authors.forename: Francesco
authors.initials: F
authors.lastname: Tedesco
authors.forename: Annunciata
authors.initials: A
authors.lastname: Vecchi
authors.forename: Sergio A
authors.initials: SA
authors.lastname: Lira
authors.forename: Massimo
authors.initials: M
authors.lastname: Locati
authors.forename: Alberto
authors.initials: A
authors.lastname: Mantovani
mesh_terms: 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
chemical_list: D017152:Antibodies, Antiphospholipid; D019742:Chemokines, CC; D008070:Lipopolysaccharides; D054447:Receptors, CCR10; D019707:Receptors, Chemokine; D000097628:Chemokine Receptor D6