Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/134679
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Type: | Journal article |
Title: | NK cell–derived GM-CSF potentiates inflammatory arthritis and is negatively regulated by CIS |
Author: | Louis, 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. |
Citation: | Journal of Experimental Medicine, 2020; 217(5):e20191421-1-e20191421-19 |
Publisher: | Rockefeller University Press |
Issue Date: | 2020 |
ISSN: | 0022-1007 1540-9538 |
Statement of Responsibility: | Cynthia Louis, Fernando Souza-Fonseca-Guimaraes, Yuyan Yang, Damian D, Silva, Tobias Kratina, Laura Dagley, Soroor Hediyeh-Zadeh, Jai Rautela, Seth Lucian Masters, Melissa J. Davis, Jeffrey J. Babon, Bogoljub Ciric, Eric Vivier, Warren S. Alexander, Nicholas D. Huntington, and Ian P. Wicks |
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. |
Keywords: | Autoimmunity, Innate immunity and inflammation |
Rights: | © 2020 Louis et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/). |
DOI: | 10.1084/jem.20191421 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/1140406 http://purl.org/au-research/grants/nhmrc/1154325 http://purl.org/au-research/grants/nhmrc/1058344 http://purl.org/au-research/grants/nhmrc/1124788 http://purl.org/au-research/grants/nhmrc/1124784 http://purl.org/au-research/grants/nhmrc/1066770 http://purl.org/au-research/grants/nhmrc/1124907 http://purl.org/au-research/grants/nhmrc/1113577 http://purl.org/au-research/grants/nhmrc/1057852 http://purl.org/au-research/grants/nhmrc/1088703 |
Published version: | http://dx.doi.org/10.1084/jem.20191421 |
Appears in Collections: | Medicine publications |
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