NK cell-derived GM-CSF potentiates inflammatory arthritis and is negatively regulated by CIS

Louis, C; Guimaraes, F; Yang, Y; D&#39;Silva, D; Kratina, T; Dagley, L; Hediyeh-Zadeh, S; Rautela, J; Masters, SL; Davis, MJ; Babon, JJ; Ciric, B; Vivier, E; Alexander, WS; Huntington, ND; Wicks, IP

Author(s): Louis, C; Guimaraes, F; Yang, Y; D'Silva, D; Kratina, T; Dagley, L; Hediyeh-Zadeh, S; Rautela, J; Masters, SL; Davis, MJ; Babon, JJ; Ciric, B; Vivier, E; Alexander, WS; Huntington, ND; Wicks, IP;
Details: Publication Year 2020-05-04,Volume 217,Issue #5,Page e20191421
Journal Title: Journal of Experimental Medicine
Publication Type: Journal Article
Abstract: Despite 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.
Publisher: Rockefeller University Press
Research Division(s): Blood Cells And Blood Cancer; Structural Biology; Immunology; Inflammation; Advanced Technology And Biology; Bioinformatics
PubMed ID: 32097462
Publisher's Version: https://doi.org/10.1084/jem.20191421
Open Access at Publisher's Site: https://doi.org/10.1084/jem.20191421
NHMRC Grants: NHMRC/1113577, NHMRC/1124784, NHMRC/1066770, NHMRC/1057852, NHMRC/1124907, NHMRC/1140406, NHMRC/1124788, NHMRC/1058344,
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Creation Date: 2020-03-24 01:39:41

Last Modified: 2020-03-24 02:15:44