title: CXCR3/CXCL10 Axis Regulates Neutrophil-NK Cell Cross-Talk Determining the Severity of Experimental Osteoarthritis.
abstract: Several immune cell populations are involved in cartilage damage, bone erosion, and resorption processes during osteoarthritis. The purpose of this study was to investigate the role of NK cells in the pathogenesis of experimental osteoarthritis and whether and how neutrophils can regulate their synovial localization in the disease. Experimental osteoarthritis was elicited by intra-articular injection of collagenase in wild type andCxcr3-/-8-wk old mice. To follow osteoarthritis progression, cartilage damage, synovial thickening, and osteophyte formation were measured histologically. To characterize the inflammatory cells involved in osteoarthritis, synovial fluid was collected early after disease induction, and the cellular and cytokine content were quantified by flow cytometry and ELISA, respectively. We found that NK cells and neutrophils are among the first cells that accumulate in the synovium during osteoarthritis, both exerting a pathogenic role. Moreover, we uncovered a crucial role of the CXCL10/CXCR3 axis, with CXCL10 increasing in synovial fluids after injury andCxcr3-/-mice being protected from disease development. Finally, in vivo depletion experiments showed that neutrophils are involved in an NK cell increase in the synovium, possibly by expressing CXCL10 in inflamed joints. Thus, neutrophils and NK cells act as important disease-promoting immune cells in experimental osteoarthritis and their functional interaction is promoted by the CXCL10/CXCR3 axis.
authors.affiliation: Department of Molecular Medicine, Sapienza University of Rome, 00161 Rome, Italy.
authors.forename: Giorgia
authors.initials: G
authors.lastname: Benigni
authors.affiliation: Department of Immunology, Institute of Microbiology, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria.
authors.forename: Petya
authors.identifier: 0000-0003-0920-3712
authors.initials: P
authors.lastname: Dimitrova
authors.affiliation: Department of Molecular Medicine, Sapienza University of Rome, 00161 Rome, Italy.
authors.forename: Fabrizio
authors.identifier: 0000-0002-6369-2249
authors.initials: F
authors.lastname: Antonangeli
authors.affiliation: Department of Molecular Medicine, Sapienza University of Rome, 00161 Rome, Italy.
authors.forename: Emilio
authors.identifier: 0000-0002-2643-0573
authors.initials: E
authors.lastname: Sanseviero
authors.affiliation: Department of Immunology, Institute of Microbiology, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria.
authors.forename: Viktoriya
authors.identifier: 0000-0002-3578-4744
authors.initials: V
authors.lastname: Milanova
authors.affiliation: Department of Rheumatology, Radboud University Medical Center, Nijmegen 86525, the Netherlands.
authors.forename: Arjen
authors.initials: A
authors.lastname: Blom
authors.affiliation: Department of Rheumatology, Radboud University Medical Center, Nijmegen 86525, the Netherlands.
authors.forename: Peter
authors.initials: P
authors.lastname: van Lent
authors.affiliation: Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, Italy.
authors.forename: Stefania
authors.identifier: 0000-0003-2441-9749
authors.initials: S
authors.lastname: Morrone
authors.affiliation: Laboratory of Immunology and Molecular Immunopathology Institute Pasteur Italy-Cenci Bolognetti Foundation, Department of Molecular Medicine, Sapienza University of Rome, 00161 Rome, Italy; and angela.santoni@uniroma1.it.|Istituto di Ricovero e Cura a Carattere Scientifico, Neuromed, Pozzilli, 86077 Isernia, Italy.
authors.forename: Angela
authors.identifier: 0000-0003-1206-7731
authors.initials: A
authors.lastname: Santoni
authors.affiliation: Department of Molecular Medicine, Sapienza University of Rome, 00161 Rome, Italy.|Istituto di Ricovero e Cura a Carattere Scientifico, Neuromed, Pozzilli, 86077 Isernia, Italy.
authors.forename: Giovanni
authors.identifier: 0000-0002-3705-2598
authors.initials: G
authors.lastname: Bernardini
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology*; D002356:Cartilage / Q000473:pathology; D054357:Chemokine CXCL10 / Q000378:metabolism*; D017364:Collagenases / Q000276:immunology; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology*; D010003:Osteoarthritis / Q000276:immunology*; D020239:Receptor Cross-Talk; D054367:Receptors, CXCR3 / Q000235:genetics / Q000378:metabolism*; D013583:Synovial Membrane / Q000276:immunology*
chemical_list: D054357:Chemokine CXCL10; C515188:Cxcr3 protein, mouse; D054367:Receptors, CXCR3; D017364:Collagenases