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dc.contributor.authorLouis, C
dc.contributor.authorSouza-Fonseca-Guimaraes, F
dc.contributor.authorYang, Y
dc.contributor.authorD'Silva, D
dc.contributor.authorKratina, T
dc.contributor.authorDagley, L
dc.contributor.authorHediyeh-Zadeh, S
dc.contributor.authorRautela, J
dc.contributor.authorMasters, SL
dc.contributor.authorDavis, MJ
dc.contributor.authorBabon, JJ
dc.contributor.authorCiric, B
dc.contributor.authorVivier, E
dc.contributor.authorAlexander, WS
dc.contributor.authorHuntington, ND
dc.contributor.authorWicks, IP
dc.date.accessioned2020-11-17T03:13:54Z
dc.date.available2020-11-17T03:13:54Z
dc.date.issued2020-05-01
dc.identifierpii: 133838
dc.identifier.citationLouis, C., Souza-Fonseca-Guimaraes, F., Yang, Y., D'Silva, D., Kratina, T., Dagley, L., Hediyeh-Zadeh, S., Rautela, J., Masters, S. L., Davis, M. J., Babon, J. J., Ciric, B., Vivier, E., Alexander, W. S., Huntington, N. D. & Wicks, I. P. (2020). NK cell-derived GM-CSF potentiates inflammatory arthritis and is negatively regulated by CIS. JOURNAL OF EXPERIMENTAL MEDICINE, 217 (5), https://doi.org/10.1084/jem.20191421.
dc.identifier.issn0022-1007
dc.identifier.urihttp://hdl.handle.net/11343/251450
dc.description.abstractDespite increasing recognition of the importance of GM-CSF in autoimmune disease, it remains unclear how GM-CSF is regulated at sites of tissue inflammation. Using GM-CSF fate reporter mice, we show that synovial NK cells produce GM-CSF in autoantibody-mediated inflammatory arthritis. Synovial NK cells promote a neutrophilic inflammatory cell infiltrate, and persistent arthritis, via GM-CSF production, as deletion of NK cells, or specific ablation of GM-CSF production in NK cells, abrogated disease. Synovial NK cell production of GM-CSF is IL-18-dependent. Furthermore, we show that cytokine-inducible SH2-containing protein (CIS) is crucial in limiting GM-CSF signaling not only during inflammatory arthritis but also in experimental allergic encephalomyelitis (EAE), a murine model of multiple sclerosis. Thus, a cellular cascade of synovial macrophages, NK cells, and neutrophils mediates persistent joint inflammation via production of IL-18 and GM-CSF. Endogenous CIS provides a key brake on signaling through the GM-CSF receptor. These findings shed new light on GM-CSF biology in sterile tissue inflammation and identify several potential therapeutic targets.
dc.languageEnglish
dc.publisherROCKEFELLER UNIV PRESS
dc.titleNK cell-derived GM-CSF potentiates inflammatory arthritis and is negatively regulated by CIS
dc.typeJournal Article
dc.identifier.doi10.1084/jem.20191421
melbourne.affiliation.departmentMedical Biology (W.E.H.I.)
melbourne.affiliation.departmentMedicine and Radiology
melbourne.source.titleJournal of Experimental Medicine
melbourne.source.volume217
melbourne.source.issue5
dc.rights.licenseCC BY-NC-SA
melbourne.elementsid1438935
melbourne.contributor.authorBabon, Jeffrey
melbourne.contributor.authorAlexander, Warren
melbourne.contributor.authorHuntington, Nicholas
melbourne.contributor.authorDavis, Melissa
melbourne.contributor.authorMasters, Seth
melbourne.contributor.authorRautela, Jai
melbourne.contributor.authorLouis, Cynthia
melbourne.contributor.authorWicks, Ian
melbourne.contributor.authorDagley, Laura
melbourne.contributor.authorFonseca Guimaraes, Fernando
dc.identifier.eissn1540-9538
melbourne.accessrightsOpen Access


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