Details

Autor(en) / Beteiligte

• 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
• Wicks, Ian P

Titel

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

Ist Teil von

• The Journal of experimental medicine, 2020-05, Vol.217 (5)

Ort / Verlag

United States: Rockefeller University Press

Erscheinungsjahr

2020

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.