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Nat Commun. 2016 Apr 1;7:11004. doi: 10.1038/ncomms11004.

Neutrophil-specific deletion of the CARD9 gene expression regulator suppresses autoantibody-induced inflammation in vivo.

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Department of Physiology, Semmelweis University School of Medicine, 1094 Budapest, Hungary.
MTA-SE 'Lendület' Inflammation Physiology Research Group of the Hungarian Academy of Sciences and Semmelweis University, 1094 Budapest, Hungary.
Department of Dermatology, University Hospital Freiburg and BIOSS Centre for Biological Signalling Studies, 79104 Freiburg, Germany.
Department of Clinical Chemistry and Pathobiochemistry, Technical University of Munich, 81675 Munich, Germany.


Neutrophils are terminally differentiated cells with limited transcriptional activity. The biological function of their gene expression changes is poorly understood. CARD9 regulates transcription during antifungal immunity but its role in sterile inflammation is unclear. Here we show that neutrophil CARD9 mediates pro-inflammatory chemokine/cytokine but not lipid mediator release during non-infectious inflammation. Genetic deficiency of CARD9 suppresses autoantibody-induced arthritis and dermatitis in mice. Neutrophil-specific deletion of CARD9 is sufficient to induce that phenotype. Card9(-/-) neutrophils show defective immune complex-induced gene expression changes and pro-inflammatory chemokine/cytokine release but normal LTB4 production and other short-term responses. In vivo deletion of CARD9 reduces tissue levels of pro-inflammatory chemokines and cytokines but not LTB4. The CARD9-mediated signalling pathway involves Src-family kinases, Syk, PLCγ2, Bcl10/Malt1 and NFκB. Collectively, CARD9-mediated gene expression changes within neutrophils play important roles during non-infectious inflammation in vivo and CARD9 acts as a divergence point between chemokine/cytokine and lipid mediator release.

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