CXCR3/CXCL10 axis regulates neutrophil-nk cell cross-talk determining the severity of experimental osteoarthritis

Giorgia Benigni, Petya Dimitrova, Fabrizio Antonangeli, Emilio Sanseviero, Viktoriya Milanova, Arjen Blom, Peter Van Lent, Stefania Morrone, Angela Santoni, Giovanni Bernardini

Research output: Contribution to journalArticle

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 intraarticular injection of collagenase in wild type and Cxcr32/2 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 and Cxcr32/2 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 diseasepromoting immune cells in experimental osteoarthritis and their functional interaction is promoted by the CXCL10/CXCR3 axis.

Original languageEnglish
Pages (from-to)2115-2124
Number of pages10
JournalJournal of Immunology
Volume198
Issue number5
DOIs
Publication statusPublished - Mar 1 2017

    Fingerprint

ASJC Scopus subject areas

  • Immunology

Cite this

Benigni, G., Dimitrova, P., Antonangeli, F., Sanseviero, E., Milanova, V., Blom, A., Van Lent, P., Morrone, S., Santoni, A., & Bernardini, G. (2017). CXCR3/CXCL10 axis regulates neutrophil-nk cell cross-talk determining the severity of experimental osteoarthritis. Journal of Immunology, 198(5), 2115-2124. https://doi.org/10.4049/jimmunol.1601359