| First Author | Louis C | Year | 2020 |
| Journal | J Exp Med | Volume | 217 |
| Issue | 5 | PubMed ID | 32097462 |
| Mgi Jnum | J:289419 | Mgi Id | MGI:6432670 |
| Doi | 10.1084/jem.20191421 | Citation | Louis C, et al. (2020) NK cell-derived GM-CSF potentiates inflammatory arthritis and is negatively regulated by CIS. J Exp Med 217(5) |
| abstractText | 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. |
