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

Author

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  • Tamás Németh

    (Semmelweis University School of Medicine
    MTA-SE ‘Lendület’ Inflammation Physiology Research Group of the Hungarian Academy of Sciences and Semmelweis University)

  • Krisztina Futosi

    (Semmelweis University School of Medicine)

  • Cassian Sitaru

    (University Hospital Freiburg and BIOSS Centre for Biological Signalling Studies)

  • Jürgen Ruland

    (Technical University of Munich)

  • Attila Mócsai

    (Semmelweis University School of Medicine
    MTA-SE ‘Lendület’ Inflammation Physiology Research Group of the Hungarian Academy of Sciences and Semmelweis University)

Abstract

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.

Suggested Citation

  • Tamás Németh & Krisztina Futosi & Cassian Sitaru & Jürgen Ruland & Attila Mócsai, 2016. "Neutrophil-specific deletion of the CARD9 gene expression regulator suppresses autoantibody-induced inflammation in vivo," Nature Communications, Nature, vol. 7(1), pages 1-13, April.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms11004
    DOI: 10.1038/ncomms11004
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    Cited by:

    1. Yao Yu & Rong-Rong Wang & Nai-Jun Miao & Jia-Jie Tang & Yun-Wei Zhang & Xiang-Ran Lu & Pei-Yi Yan & Jing Wang & Xin-Ming Jia, 2022. "PD-L1 negatively regulates antifungal immunity by inhibiting neutrophil release from bone marrow," Nature Communications, Nature, vol. 13(1), pages 1-16, December.

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