Dysregulation of Inflammasome Priming and Activation by MicroRNAs in Human Immune-Mediated Diseases

J Immunol. 2019 Apr 15;202(8):2177-2187. doi: 10.4049/jimmunol.1801416.

Abstract

Inflammasomes are protein complexes that respond to a wide range of pathogens and cellular damage signals. Their activation prompts the caspase-1-mediated cleavage of the proinflammatory cytokines IL-1β and IL-18. Inflammasome dysregulation has been demonstrated to play a role in a range of diseases involving the adaptive immune system like multiple sclerosis, rheumatic diseases, and type 1 diabetes. Priming and activation of inflammasomes can be modulated by microRNAs (miRNAs), small noncoding RNAs that regulate gene expression posttranscriptionally. miRNAs, such as miR-223-3p, have been demonstrated to directly target the inflammasome components NLRP3, caspase-1, and caspase-8. Other miRNAs like miR-155-5p modulate TLR-, IL-1R-, TNFR-, and IFNAR-mediated signaling pathways upstream of the inflammasomes. In this study, we discuss how a more detailed elucidation of miRNA-driven inflammasome regulation helps in understanding the molecular processes underlying immune-mediated human diseases, holds potential for the identification of biomarkers and may offer novel targets for the development of future therapeutics.

Publication types

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

MeSH terms

  • Autoimmune Diseases / immunology*
  • Autoimmune Diseases / pathology
  • Caspase 1 / immunology
  • Caspase 8 / immunology
  • Humans
  • Inflammasomes / immunology*
  • MicroRNAs / immunology*
  • NLR Family, Pyrin Domain-Containing 3 Protein / immunology
  • Receptors, Interleukin / immunology
  • Signal Transduction / immunology*
  • Toll-Like Receptors / immunology

Substances

  • Inflammasomes
  • MIRN155 microRNA, human
  • MIRN223 microRNA, human
  • MicroRNAs
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • NLRP3 protein, human
  • Receptors, Interleukin
  • Toll-Like Receptors
  • CASP8 protein, human
  • Caspase 8
  • Caspase 1