| Title: |
NK cell–derived GM-CSF potentiates inflammatory arthritis and is negatively regulated by CIS |
| Authors: |
Louis, C; Souza-Fonseca-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 |
| Publisher Information: |
ROCKEFELLER UNIV PRESS |
| Publication Year: |
2020 |
| Collection: |
The University of Melbourne: Digital Repository |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| ISSN: |
0022-1007 |
| Relation: |
pii: 133838; https://hdl.handle.net/11343/251450 |
| Availability: |
https://hdl.handle.net/11343/251450 |
| Rights: |
https://creativecommons.org/licenses/by-nc-sa/4.0 ; CC BY-NC-SA |
| Accession Number: |
edsbas.6442B3C5 |
| Database: |
BASE |