TY  - JOUR
AU  - Louis, C
AU  - Souza-Fonseca-Guimaraes, F
AU  - Yang, Y
AU  - D'Silva, D
AU  - Kratina, T
AU  - Dagley, L
AU  - Hediyeh-Zadeh, S
AU  - Rautela, J
AU  - Masters, SL
AU  - Davis, MJ
AU  - Babon, JJ
AU  - Ciric, B
AU  - Vivier, E
AU  - Alexander, WS
AU  - Huntington, ND
AU  - Wicks, IP
Y2  - 2020/11/17
Y1  - 2020/05/01
SN  - 0022-1007
UR  - http://hdl.handle.net/11343/251450
AB  - 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.
LA  - English
PB  - ROCKEFELLER UNIV PRESS
T1  - NK cell-derived GM-CSF potentiates inflammatory arthritis and is negatively regulated by CIS
DO  - 10.1084/jem.20191421
IS  - Journal of Experimental Medicine
VL  - 217
IS  - 5
L1  - /bitstream/handle/11343/251450/PMC7201918.pdf?sequence=1&isAllowed=y
ER  -