The inflammasomes: the key regulators of inflammation.
Following any threat to tissutal integrity, innate immune system promptly recognizes foreign/damage-associated molecules and orchestrates the global immune response, inducing inflammation, chemotaxis, phagocytosis and production of antimicrobial effector molecules, as well as providing instruction to the adaptive immune system. Innate immune cells detect both exogenous and endogenous danger signals through invariant germline-encoded pattern recognition receptors, including Toll-like receptors, retinoic acid-inducible gene I-like receptors, and nucleotide binding domain and leucine reach repeat containing receptors (NLRs). The recruitment of NLRs, namely IPAF, NAIPs and NALPs, by various potentially harmful stimuli leads to the assembly of inflammasomes, multimeric caspase-activating complexes entailing the sensor NLR, intracellular adaptor proteins, and procaspase-1 and -5. The caspase activation is necessarily required for the processing and secretion of proinflammatory cytokines, such as interleukin (IL)-1b, IL-18, and IL-33. Therefore, the inflammasomes are critical regulators of the inflammatory response. Dysregulation of such a versatile sentry system is involved in the pathogenesis of human autoinflammatory diseases, autoimmune disorders, and microcrystalline arthritides. A better knowledge of the inflammasome crucial role in the immune response may provide possible future therapeutic improvements in protection against invading pathogens and in vaccine efficacy, as well as in the treatment of human inflammatory diseases.
Dipartimento Medico-Specialistico 2 - S.D. di Medicina Interna e Reumatologia Azienda Ospedaliero-Universitaria di Parma, Via Gramsci 14, 43100 Parma (Italy).
Pieranna
P
Fietta
Giovanni
G
Delsante
D053468:CARD Signaling Adaptor Proteins / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000276:immunology*
D053468:CARD Signaling Adaptor Proteins