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The monogenic autoinflammatory diseases define new pathways in human innate immunity and inflammation

A Corrigendum to this article was published on 18 October 2017

This article has been updated

Abstract

Autoinflammatory diseases were first recognized nearly 20 years ago as distinct clinical and immunological entities caused by dysregulation in the innate immune system. Since then, advances in genomic techniques have led to the identification of new monogenic disorders and their corresponding signaling pathways. Here we review these monogenic autoinflammatory diseases, ranging from periodic fever syndromes caused by dysregulated inflammasome-mediated production of the cytokine IL-1β to disorders arising from perturbations in signaling by the transcription factor NF-κB, ubiquitination, cytokine signaling, protein folding, type I interferon production and complement activation, and we further examine their molecular mechanisms. We also explore the overlap among autoinflammation, autoimmunity and immunodeficiency, and pose a series of unanswered questions that are expected to be central in autoinflammatory disease research in the coming decade.

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Figure 1: Mechanisms of autoinflammatory diseases mediated by activated inflammasomes and IL-1β-production pathways.
Figure 2: Mechanisms of autoinflammatory diseases mediated by the NF-κB pathway.
Figure 3: Mechanisms of autoinflammatory diseases mediated by the complement pathway.
Figure 4: Mechanisms of autoinflammatory diseases mediated by the type I interferon pathway.

Change history

  • 17 August 2017

    In the version of this article initially published, the final sentence of the third paragraph of the first subsection ('Monogenic periodic fever syndromes') incorrectly states that "Colchicine causes microtubule destabilization, thereby facilitating pyrin-inflammasome activation independently of RhoA." That sentence should read: "Colchicine also causes microtubule destabilization, thereby inhibiting pyrin-inflammasome activation independently of RhoA." The error has been corrected in the HTML and PDF versions of the article.

  • 18 October 2017

    Nat. Immunol. 18, 832–842 (2017); published online 19 July 2017; corrected after print 17 August 2017 In the version of this article initially published, the final sentence of the third paragraph of the first subsection ('Monogenic periodic fever syndromes') incorrectly states that “Colchicine causes microtubule destabilization, thereby facilitating pyrin-inflammasome activation independently of RhoA.

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Correspondence to Kalpana Manthiram or Daniel L Kastner.

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Manthiram, K., Zhou, Q., Aksentijevich, I. et al. The monogenic autoinflammatory diseases define new pathways in human innate immunity and inflammation. Nat Immunol 18, 832–842 (2017). https://doi.org/10.1038/ni.3777

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