The inflammasome and lupus: another innate immune mechanism contributing to disease pathogenesis?

Curr Opin Rheumatol. 2014 Sep;26(5):475-81. doi: 10.1097/BOR.0000000000000088.


Purpose of review: The role of innate immunity in systemic lupus erythematosus (SLE) has been a rapidly expanding area of research over the last decade. Included in this rubric is the concept that activation of the inflammasome, a molecular complex that activates caspase-1 and in turn the cytokines IL-1β and IL-18, is important in lupus pathogenesis. This review will summarize the recent discoveries exploring the role of the inflammasome machinery in SLE.

Recent findings: Immune complexes can activate the NLRP3 inflammasome, and SLE-derived macrophages are hyper-responsive to innate immune stimuli, leading to enhanced activation of the inflammasome and production of inflammatory cytokines. Work in several murine models suggests an important role for the NLRP3 inflammasome in mediating lupus nephritis. Caspase-1, the central enzyme of the inflammasome, is essential for the development of type I interferon responses, autoantibody production, and nephritis in the pristane model of lupus. The absence of melanoma 2 inflammasome may have protective and pathogenic roles in SLE.

Summary: Recent evidence suggests that the inflammasome machinery is dysregulated in SLE, plays an important role in promotion of organ damage, and may mediate cross-talk between environmental triggers and the development of lupus. Further research should focus on whether inhibition of inflammasome components may serve as a viable target for therapeutic development in SLE.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cardiovascular Diseases / etiology
  • Cardiovascular Diseases / immunology
  • Carrier Proteins / metabolism
  • Caspase 1 / metabolism
  • Cytokines / metabolism
  • Humans
  • Immunity, Innate*
  • Inflammasomes / genetics
  • Inflammasomes / immunology*
  • Inflammasomes / metabolism
  • Interleukin-18 / metabolism
  • Interleukin-1beta / metabolism
  • Lupus Erythematosus, Cutaneous / etiology
  • Lupus Erythematosus, Cutaneous / immunology
  • Lupus Erythematosus, Systemic / etiology*
  • Lupus Erythematosus, Systemic / immunology*
  • Lupus Erythematosus, Systemic / metabolism
  • Lupus Nephritis / etiology
  • Lupus Nephritis / immunology
  • Mice
  • Models, Immunological
  • NLR Family, Pyrin Domain-Containing 3 Protein


  • Carrier Proteins
  • Cytokines
  • Inflammasomes
  • Interleukin-18
  • Interleukin-1beta
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • NLRP3 protein, human
  • Caspase 1