Inflammasome-Dependent Cytokines at the Crossroads of Health and Autoinflammatory Disease

Cold Spring Harb Perspect Biol. 2019 Jan 2;11(1):a028563. doi: 10.1101/cshperspect.a028563.

Abstract

As key regulators of both innate and adaptive immunity, it is unsurprising that the activity of interleukin (IL)-1 cytokine family members is tightly controlled by decoy receptors, antagonists, and a variety of other mechanisms. Additionally, inflammasome-mediated proteolytic maturation is a prominent and distinguishing feature of two important members of this cytokine family, IL-1β and IL-18, because their full-length gene products are biologically inert. Although vital in antimicrobial host defense, deregulated inflammasome signaling is linked with a growing number of autoimmune and autoinflammatory diseases. Here, we focus on introducing the diverse inflammasome types and discussing their causal roles in periodic fever syndromes. Therapies targeting IL-1 or IL-18 show great efficacy in some of these autoinflammatory diseases, although further understanding of the molecular mechanisms leading to unregulated production of these key cytokines is required to benefit more patients.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptive Immunity
  • Anemia, Dyserythropoietic, Congenital / immunology
  • Animals
  • Autoimmune Diseases
  • Autoimmunity
  • Carrier Proteins / immunology
  • Cryopyrin-Associated Periodic Syndromes / immunology
  • Familial Mediterranean Fever / immunology
  • Fever / immunology
  • HMGB1 Protein / metabolism
  • Humans
  • Immune System
  • Immunity, Innate
  • Immunologic Deficiency Syndromes / immunology
  • Inflammasomes / immunology*
  • Inflammation
  • Interleukin 1 Receptor Antagonist Protein / immunology
  • Interleukin-18 / immunology*
  • Interleukin-1beta / immunology*
  • Mice
  • Models, Biological
  • Osteomyelitis / immunology
  • Pyroptosis
  • S100 Proteins / metabolism
  • Signal Transduction

Substances

  • Carrier Proteins
  • HMGB1 Protein
  • HMGB1 protein, human
  • IL18 protein, human
  • IL1B protein, human
  • IL1RN protein, human
  • Inflammasomes
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-18
  • Interleukin-1beta
  • S100 Proteins

Supplementary concepts

  • Majeed syndrome