Journal article

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

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, Ian P Wicks

Journal of Experimental Medicine | ROCKEFELLER UNIV PRESS | Published : 2020

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 inflamm..

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Grants

Awarded by National Health and Medical Research Council of Australia


Awarded by National Health and Medical Research Council Medical Research Future Fund Practitioner Fellowship


Awarded by National Health and Medical Research Council


Awarded by National Breast Cancer Foundation Fellowship


Awarded by Priority-Driven Collaborative Cancer Research Scheme


Funding Acknowledgements

This work is supported by grants from the National Health and Medical Research Council of Australia (1113577 to W.S. Alexander and I.P. Wicks; 1124784, 1066770, 1057852, and 1124907 to N.D. Huntington; and 1140406 to F. Souza-Fonseca-Guimaraes) and John T. Reid Charitable Trusts to I.P. Wicks. I.P. Wicks is supported by a National Health and Medical Research Council Medical Research Future Fund Practitioner Fellowship (1154325). F. Souza-Fonseca-Guimaraes was supported by a National Health and Medical Research Council Early Career Fellowship (1088703), a National Breast Cancer Foundation Fellowship (PF-15-008), and grant awarded through the Priority-Driven Collaborative Cancer Research Scheme (1120725) and funded by Cure Cancer Australia Foundation with the assistance of Cancer Australia. N.D. Huntington is a National Health and Medical Research Council CDF2 Fellow (1124788), a recipient of a Melanoma Research Grant from the Harry J. Lloyd Charitable Trust, a Melanoma Research Alliance Young Investigator Award, a Tour De Cure research grant, an equipment grant fromthe Ian Potter Foundation, and a CLIP grant from the Cancer Research Institute. W.S. Alexander is a National Health and Medical Research Council Senior Principal Research Fellow (1058344). This studywasmade possible throughVictorian State Government Operational Infrastructure Support and the Australian Government National Health and Medical Research Council Independent Research Institute Infrastructure Support scheme.