The rhapsody of NLRPs: master players of inflammation...and a lot more

Immunol Res. 2012 Sep;53(1-3):78-90. doi: 10.1007/s12026-012-8272-z.

Abstract

The Nucleotide-binding oligomerization domain, Leucine-rich Repeat and Pyrin domain containing (NLRP) family and corresponding inflammasomes are important intracellular sensors of microbial pathogens and stress signals that promote caspase-1-mediated release of IL-1β and IL-18. Studies using targeted disruption of NLRP1 and NLRP3 have revealed key roles for these inflammasomes in innate immunity and inflammation, as well as in autoimmune diseases, metabolic disorders, and cancers. The newly identified family members NLRP6, NLRP10, and NLRP12 are emerging as important molecules regulating gut homeostasis in mouse models, as well as being correlated to human diseases. Here, we review our current knowledge of NLRP1 and NLRP3 biology, from molecular structure, function, and proposed models of activation to associations with several human disorders. New insights into novel NLRPs that act as regulators of intestinal immunity are also discussed.

Publication types

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

MeSH terms

  • Adaptor Proteins, Signal Transducing / immunology*
  • Animals
  • Apoptosis Regulatory Proteins / immunology*
  • Carrier Proteins / immunology*
  • Caspase 1 / metabolism
  • Disease Models, Animal
  • Homeostasis
  • Humans
  • Immunity, Mucosal
  • Inflammasomes / immunology
  • Inflammation / immunology*
  • Interleukin-18 / metabolism
  • Interleukin-1beta / metabolism
  • Intestinal Diseases / immunology*
  • Mice
  • Multiprotein Complexes / immunology*
  • NLR Family, Pyrin Domain-Containing 3 Protein

Substances

  • Adaptor Proteins, Signal Transducing
  • Apoptosis Regulatory Proteins
  • Carrier Proteins
  • Inflammasomes
  • Interleukin-18
  • Interleukin-1beta
  • Multiprotein Complexes
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • NLRP1 protein, human
  • NLRP3 protein, human
  • Caspase 1