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

Authors

Cynthia Louis, University of Melbourne
Fernando Souza-Fonseca-Guimaraes, University of Queensland Diamantina Institute
Yuyan Yang, The Walter and Eliza Hall Institute of Medical Research
Damian D'Silva, The Walter and Eliza Hall Institute of Medical Research
Tobias Kratina, The Walter and Eliza Hall Institute of Medical Research
Laura Dagley, The Walter and Eliza Hall Institute of Medical Research
Soroor Hediyeh-Zadeh, The Walter and Eliza Hall Institute of Medical Research
Jai Rautela, Monash University
Seth Lucian Masters, University of Melbourne
Melissa J Davis, The Walter and Eliza Hall Institute of Medical Research
Jeffrey J Babon, The Walter and Eliza Hall Institute of Medical Research
Bogoljub Ciric, Thomas Jefferson UniversityFollow
Eric Vivier, Aix Marseille University
Warren S Alexander, The Walter and Eliza Hall Institute of Medical Research
Nicholas D Huntington, Monash University
Ian P Wicks, Royal Melbourne Hospital

Document Type

Article

Publication Date

5-4-2020

Comments

This article is the author’s final published version in Journal of Experimental Medicine, Volume 217, Issue 5, May 2020, Article number e20191421.

The published version is available at https://doi.org/10.1084/jem.20191421. Copyright © Loius et al.

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.

Recommended Citation

Louis, Cynthia; Souza-Fonseca-Guimaraes, Fernando; Yang, Yuyan; D'Silva, Damian; Kratina, Tobias; Dagley, Laura; Hediyeh-Zadeh, Soroor; Rautela, Jai; Masters, Seth Lucian; Davis, Melissa J; Babon, Jeffrey J; Ciric, Bogoljub; Vivier, Eric; Alexander, Warren S; Huntington, Nicholas D; and Wicks, Ian P, "NK cell-derived GM-CSF potentiates inflammatory arthritis and is negatively regulated by CIS" (2020). Department of Neurology Faculty Papers. Paper 245.
https://jdc.jefferson.edu/neurologyfp/245

Creative Commons License

This work is licensed under a Creative Commons Attribution-Noncommercial-Share Alike 4.0 License.

PubMed ID

32097462

Language

English