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

• Published in: Nature immunology Vol. 18; no. 8; pp. 832 - 842
• Main Authors: Manthiram, Kalpana, Zhou, Qing, Aksentijevich, Ivona, Kastner, Daniel L
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.08.2017; Nature Publishing Group
• Subjects: 631/250/249/1313; 631/250/249/2510; 631/250/256; Autoimmunity; Autoimmunity - immunology; Biomedicine; Cellular signal transduction; Complement activation; Complement Activation - immunology; Cytokines; Cytokines - immunology; Development and progression; Fever; Genetic aspects; Health aspects; Hereditary Autoinflammatory Diseases - genetics; Hereditary Autoinflammatory Diseases - immunology; Humans; IL-1β; Immune response; Immune system; Immunity, Innate - immunology; Immunodeficiency; Immunologic Deficiency Syndromes - immunology; Immunology; Infectious Diseases; Inflammasomes; Inflammasomes - immunology; Inflammation; Inflammation - immunology; Innate immunity; Interferon; Interferon Type I - immunology; Interleukin-1beta - immunology; Molecular modelling; NF-kappa B - immunology; NF-κB protein; Protein Folding; review-article; Signal Transduction; Transcription factors; Ubiquitination; Ubiquitination - immunology
• ISSN: 1529-2908; 1529-2916
• DOI: 10.1038/ni.3777

Kastner and colleagues review monogenic autoinflammatory diseases and their molecular mechanisms and explore the overlap among autoinflammation, autoimmunity and immunodeficiency. 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.