title: Ly6Chigh Monocytes Protect against Kidney Damage during Sepsis via a CX3CR1-Dependent Adhesion Mechanism.
abstract: Monocytes have a crucial role in both proinflammatory and anti-inflammatory phenomena occurring during sepsis. Monocyte recruitment and activation are orchestrated by the chemokine receptors CX3CR1 and CCR2 and their cognate ligands. However, little is known about the roles of these cells and chemokines during the acute phase of inflammation in sepsis. Using intravital microscopy in a murine model of polymicrobial sepsis, we showed that inflammatory Ly6C(high) monocytes infiltrated kidneys, exhibited altered motility, and adhered strongly to the renal vascular wall in a chemokine receptor CX3CR1-dependent manner. Adoptive transfer of Cx3cr1-proficient monocyte-enriched bone marrow cells into septic Cx3cr1-depleted mice prevented kidney damage and promoted mouse survival. Modulation of CX3CR1 activation in septic mice controlled monocyte adhesion, regulated proinflammatory and anti-inflammatory cytokine expression, and was associated with the extent of kidney lesions such that the number of lesions decreased when CX3CR1 activity increased. Consistent with these results, the pro-adhesive I249 CX3CR1 allele in humans was associated with a lower incidence of AKI in patients with sepsis. These data show that inflammatory monocytes have a protective effect during sepsis via a CX3CR1-dependent adhesion mechanism. This receptor might be a new therapeutic target for kidney injury during sepsis.
authors.affiliation: Sorbonne Universités, Université Pierre et Marie Curie (UPMC), University of Paris 06, Paris, France; Institut National de la Santé et de la Recherche Médicale (INSERM), U1135, Paris, France; Centre National de la Recherche Scientifique (CNRS), Paris, France; Département d'Anesthésie-Réanimation-Service d'Aide Médicale Urgente (SMUR), Hôpital Lariboisière, Assistance Publique-Hôpitaux de Paris, Paris, France;
authors.forename: Benjamin G
authors.initials: BG
authors.lastname: Chousterman
authors.affiliation: Sorbonne Universités, Université Pierre et Marie Curie (UPMC), University of Paris 06, Paris, France; Institut National de la Santé et de la Recherche Médicale (INSERM), U1135, Paris, France; Centre National de la Recherche Scientifique (CNRS), Paris, France; alexandre.boissonnas@upmc.fr christophe.combadiere@upmc.fr.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Boissonnas
authors.affiliation: Sorbonne Universités, Université Pierre et Marie Curie (UPMC), University of Paris 06, Paris, France; Institut National de la Santé et de la Recherche Médicale (INSERM), U1135, Paris, France; Centre National de la Recherche Scientifique (CNRS), Paris, France;
authors.forename: Lucie
authors.initials: L
authors.lastname: Poupel
authors.affiliation: Sorbonne Universités, Université Pierre et Marie Curie (UPMC), University of Paris 06, Paris, France; Institut National de la Santé et de la Recherche Médicale (INSERM), U1135, Paris, France; Centre National de la Recherche Scientifique (CNRS), Paris, France;
authors.forename: Camille
authors.initials: C
authors.lastname: Baudesson de Chanville
authors.affiliation: Institut Gustave-Roussy, Université Paris-Sud Villejuif, France;
authors.forename: Julien
authors.initials: J
authors.lastname: Adam
authors.affiliation: Sorbonne Universités, Université Pierre et Marie Curie (UPMC), University of Paris 06, Paris, France; Service des Explorations Fonctionnelles and Institut National de la Santé et de la Recherche Médicale, Assistance Publique-Hôpitaux de Paris, Hôpital Tenon, Paris, France; and.
authors.forename: Nahid
authors.initials: N
authors.lastname: Tabibzadeh
authors.affiliation: Sorbonne Universités, Université Pierre et Marie Curie (UPMC), University of Paris 06, Paris, France; Institut National de la Santé et de la Recherche Médicale (INSERM), U1135, Paris, France; Centre National de la Recherche Scientifique (CNRS), Paris, France;
authors.forename: Fabrice
authors.initials: F
authors.lastname: Licata
authors.affiliation: Département d'Anesthésie-Réanimation-Service d'Aide Médicale Urgente (SMUR), Hôpital Lariboisière, Assistance Publique-Hôpitaux de Paris, Paris, France; INSERM, U1160, Paris, France.
authors.forename: Anne-Claire
authors.initials: AC
authors.lastname: Lukaszewicz
authors.affiliation: Sorbonne Universités, Université Pierre et Marie Curie (UPMC), University of Paris 06, Paris, France; Institut National de la Santé et de la Recherche Médicale (INSERM), U1135, Paris, France; Centre National de la Recherche Scientifique (CNRS), Paris, France;
authors.forename: Amélie
authors.initials: A
authors.lastname: Lombès
authors.affiliation: Sorbonne Universités, Université Pierre et Marie Curie (UPMC), University of Paris 06, Paris, France; Institut National de la Santé et de la Recherche Médicale (INSERM), U1135, Paris, France; Centre National de la Recherche Scientifique (CNRS), Paris, France;
authors.forename: Philippe
authors.initials: P
authors.lastname: Deterre
authors.affiliation: Département d'Anesthésie-Réanimation-Service d'Aide Médicale Urgente (SMUR), Hôpital Lariboisière, Assistance Publique-Hôpitaux de Paris, Paris, France; INSERM, U1160, Paris, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Payen
authors.affiliation: Sorbonne Universités, Université Pierre et Marie Curie (UPMC), University of Paris 06, Paris, France; Institut National de la Santé et de la Recherche Médicale (INSERM), U1135, Paris, France; Centre National de la Recherche Scientifique (CNRS), Paris, France; alexandre.boissonnas@upmc.fr christophe.combadiere@upmc.fr.
authors.forename: Christophe
authors.initials: C
authors.lastname: Combadière
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D000210:Acute-Phase Reaction / Q000276:immunology*; D019264:Adoptive Transfer; D000483:Alleles; D000818:Animals; D000950:Antigens, Ly / Q000032:analysis; D000073883:CX3C Chemokine Receptor 1; D002448:Cell Adhesion / Q000235:genetics; D002465:Cell Movement; D004730:Endothelium, Vascular / Q000378:metabolism; D005838:Genotype; D006801:Humans; D000069416:Intravital Microscopy; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D036641:Microscopy, Fluorescence, Multiphoton; D009000:Monocytes / Q000737:chemistry / Q000502:physiology / Q000637:transplantation*; D011110:Polymorphism, Genetic; D019707:Receptors, Chemokine / Q000235:genetics* / Q000378:metabolism*; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors; D018805:Sepsis / Q000150:complications*
chemical_list: D000950:Antigens, Ly; D000073883:CX3C Chemokine Receptor 1; C095235:CX3CR1 protein, human; C471885:Cx3cr1 protein, mouse; C494192:Ly-6C antigen, mouse; D019707:Receptors, Chemokine; D017472:Receptors, Interleukin-1
keywords: chemokine receptor; immunology; kidney dysfunction