Horror Autoinflammaticus: The Molecular Pathophysiology of Autoinflammatory Disease
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TLDR
An updated classification scheme based on molecular pathophysiology will bring greater clarity to discourse while catalyzing new hypotheses both at the bench and at the bedside, supplanting a clinical classification that has served well but is opaque to the genetic, immunologic, and therapeutic interrelationships now before us.Abstract:
The autoinflammatory diseases are characterized by seemingly unprovoked episodes of inflammation, without high-titer autoantibodies or antigen-specific T cells The concept was proposed ten years ago with the identification of the genes underlying hereditary periodic fever syndromes This nosology has taken root because of the dramatic advances in our knowledge of the genetic basis of both mendelian and complex autoinflammatory diseases, and with the recognition that these illnesses derive from genetic variants of the innate immune system Herein we propose an updated classification scheme based on the molecular insights garnered over the past decade, supplanting a clinical classification that has served well but is opaque to the genetic, immunologic, and therapeutic interrelationships now before us We define six categories of autoinflammatory disease: IL-1β activation disorders (inflammasomopathies), NF-κB activation syndromes, protein misfolding disorders, complement regulatory diseases, disturbances in cytokine signaling, and macrophage activation syndromes A system based on molecular pathophysiology will bring greater clarity to our discourse while catalyzing new hypotheses both at the bench and at the bedsideread more
Citations
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Differentiation of Effector CD4 T Cell Populations
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TL;DR: It is shown that cell priming through multiple signaling receptors induces NLRP3 expression, which is identified to be a critical checkpoint for NLRP2 activation and signals provided by NF-κB activators are necessary but not sufficient forNLRP3 activation.
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The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance
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Regulation of Adaptive Immunity by the Innate Immune System
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A small-molecule inhibitor of the NLRP3 inflammasome for the treatment of inflammatory diseases
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TL;DR: MCC950 treatment rescued neonatal lethality in a mouse model of CAPS and was active in ex vivo samples from individuals with Muckle–Wells syndrome, and is a potential therapeutic for NLRP3-associated syndromes, and a tool for further study of theNLRP3 inflammasome in human health and disease.
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