title: Autophagy, NLRP3 inflammasome and auto-inflammatory/immune diseases.
abstract: Loss of homeostasis, as a result of pathogen invasion or self imbalance, causes tissue damage and inflammation. In addition to its well-established role in promoting clearance of pathogens or cell corpses, inflammation is also key to drive tissue repair and regeneration. Conserved from flies to humans, a transient, well-balanced inflammatory response is critical for restoration of tissue homeostasis after damage. The absence of such a response can result in failure of tissue repair, leading to the development of devastating immunopathologies and degenerative diseases. Studies in the past decade collectively suggest that a malfunction of NLRP3 inflammasome, a key tissue damage sensor, is a dominant driver of various autoinflammatory and autoimmune diseases, including gout, rheumatoid arthritis, and lupus. It is therefore crucial to understand the biology and regulation of NLRP3 inflammasome and determine its affect in the context of various diseases. Of note, various studies suggest that autophagy, a cellular waste removal and rejuvenation process, serves an important role as a macrophage-intrinsic negative regulator of NLRP3 inflammasome. Here, we review recent advances in understanding how autophagy regulates NLRP3 inflammasome activity and discuss the implications of this regulation on the pathogenesis of autoinflammatory and autoimmune diseases.
authors: Laboratory of Gene Regulation and Signal Transduction, Departments of Pharmacology; and Pathology, School of Medicine, University of California San Diego, La Jolla, CA, USA.
authors: Zhenyu
authors: Z
authors: Zhong
authors: Laboratory of Gene Regulation and Signal Transduction, Departments of Pharmacology; and Pathology, School of Medicine, University of California San Diego, La Jolla, CA, USA.
authors: Elsa
authors: E
authors: Sanchez-Lopez
authors: Laboratory of Gene Regulation and Signal Transduction, Departments of Pharmacology; and Pathology, School of Medicine, University of California San Diego, La Jolla, CA, USA. karinoffice@ucsd.edu.
authors: Michael
authors: M
authors: Karin
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D001327:Autoimmune Diseases / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D001343:Autophagy / Q000187:drug effects; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D006801:Humans; D058847:Inflammasomes / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000378:metabolism; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism; D008928:Mitochondria / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D063306:Mitophagy; D058990:Molecular Targeted Therapy; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D058847:Inflammasomes; D018836:Inflammation Mediators; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human