Proteomics

Dataset Information

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NK cell-derived GM-CSF is critical for enhancing pathological arthritis


ABSTRACT: GM-CSF is involved in immune complex (IC)-mediated arthritis. However, little is known about what is the cellular source of GM-CSF and how it is regulated during IC-mediated inflammation. Using novel GM-CSF reporter mice, we show that NK cells produce GM-CSF during an IC-mediated model of inflammatory arthritis. NK cells promoted STIA in a GM-CSF-dependent manner, as deletion of NK cells and selective removal of GM-CSF production by NK cells abrogated disease. Furthermore, we show that myeloid cell activation by GM-CSF is restrained by induction of JAK/STAT checkpoint inhibitor cytokine-inducible SH2-containing protein, CIS. Myeloid cells from CIS-deficient mice had exaggerated responses to GM-CSF, and these mice develop exacerbated STIA. Our data suggest that tissue NK cells may amplify joint inflammation in arthritis via GM-CSF production and thus represent a novel target in IC-mediated pathology. Endogenous CIS provides a key brake on signaling through the GM-CSF receptor and strategies that boost its function may provide an alternative anti-inflammatory approach.

INSTRUMENT(S): impact II

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Neutrophil

SUBMITTER: Laura Dagley  

LAB HEAD: Fernando Souza-Fonseca-Guimaraes

PROVIDER: PXD012794 | Pride | 2020-02-19

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
P3536_CIS24hrGM_1_1_1_1_01_9818.d.zip Other
P3536_CIS24hrGM_1_2_1_1_01_9819.d.zip Other
P3536_CIS24hrGM_1_3_1_1_01_9821.d.zip Other
P3536_CIS24hrG_1_1_1_1_01_9810.d.zip Other
P3536_CIS24hrG_1_2_1_1_01_9811.d.zip Other
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Publications


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 dise  ...[more]

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