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The E3 ubiquitin ligase Pellino2 mediates priming of the NLRP3 inflammasome

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  • Fiachra Humphries

    (National University of Ireland Maynooth, Maynooth)

  • Ronan Bergin

    (National University of Ireland Maynooth, Maynooth)

  • Ruaidhri Jackson

    (National University of Ireland Maynooth, Maynooth)

  • Nezira Delagic

    (National University of Ireland Maynooth, Maynooth)

  • Bingwei Wang

    (National University of Ireland Maynooth, Maynooth)

  • Shuo Yang

    (National University of Ireland Maynooth, Maynooth
    Nanjing Medical University)

  • Alice V. Dubois

    (Queen’s University Belfast)

  • Rebecca J. Ingram

    (Queen’s University Belfast)

  • Paul N. Moynagh

    (National University of Ireland Maynooth, Maynooth
    Queen’s University Belfast)

Abstract

The NLRP3 inflammasome has an important function in inflammation by promoting the processing of pro-IL-1β and pro-IL-18 to their mature bioactive forms, and by inducing cell death via pyroptosis. Here we show a critical function of the E3 ubiquitin ligase Pellino2 in facilitating activation of the NLRP3 inflammasome. Pellino2-deficient mice and myeloid cells have impaired activation of NLRP3 in response to toll-like receptor priming, NLRP3 stimuli and bacterial challenge. These functions of Pellino2 in the NLRP3 pathway are dependent on Pellino2 FHA and RING-like domains, with Pellino2 promoting the ubiquitination of NLRP3 during the priming phase of activation. We also identify a negative function of IRAK1 in the NLRP3 inflammasome, and describe a counter-regulatory relationship between IRAK1 and Pellino2. Our findings reveal a Pellino2-mediated regulatory signaling system that controls activation of the NLRP3 inflammasome.

Suggested Citation

  • Fiachra Humphries & Ronan Bergin & Ruaidhri Jackson & Nezira Delagic & Bingwei Wang & Shuo Yang & Alice V. Dubois & Rebecca J. Ingram & Paul N. Moynagh, 2018. "The E3 ubiquitin ligase Pellino2 mediates priming of the NLRP3 inflammasome," Nature Communications, Nature, vol. 9(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03669-z
    DOI: 10.1038/s41467-018-03669-z
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    Cited by:

    1. Kaiser Wani & Hind AlHarthi & Amani Alghamdi & Shaun Sabico & Nasser M. Al-Daghri, 2021. "Role of NLRP3 Inflammasome Activation in Obesity-Mediated Metabolic Disorders," IJERPH, MDPI, vol. 18(2), pages 1-21, January.

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