title: Causes and consequences of endoplasmic reticulum stress in rheumatic disease.
abstract: Rheumatic diseases represent a heterogeneous group of inflammatory conditions, many of which involve chronic activation of both innate and adaptive immune responses by multiple genetic and environmental factors. These immune responses involve the secretion of excessive amounts of cytokines and other signalling mediators by activated immune cells. The endoplasmic reticulum (ER) is the cellular organelle that directs the folding, processing and trafficking of membrane-bound and secreted proteins, including many key components of the immune response. Maintaining homeostasis in the ER is critical to cell function and survival. Consequently, elaborate mechanisms have evolved to sense and respond to ER stress through three main signalling pathways that together comprise the unfolded protein response (UPR). Activation of the UPR can rapidly resolve the accumulation of misfolded proteins, direct permanent changes in the size and function of cells during differentiation, and critically influence the immune response and inflammation. Recognition of the importance of ER stress and UPR signalling pathways in normal and dysregulated immune responses has greatly increased in the past few years. This Review discusses several settings in which ER stress contributes to the pathogenesis of rheumatic diseases and considers some of the therapeutic opportunities that these discoveries provide.
authors.affiliation: Pediatric Translational Research Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health, Building 10, Room 12N248B,10 Center Drive, Bethesda, Maryland 20892, USA.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Navid
authors.affiliation: Pediatric Translational Research Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health, Building 10, Room 12N248B,10 Center Drive, Bethesda, Maryland 20892, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Colbert
mesh_terms: D051702:Activating Transcription Factor 6 / Q000378:metabolism; D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology / Q000503:physiopathology*; D001402:B-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000502:physiology*; D060746:Endoplasmic Reticulum-Associated Degradation; D004722:Endoribonucleases / Q000378:metabolism; D015796:HLA-B27 Antigen / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000276:immunology / Q000378:metabolism; D006801:Humans; D032389:Myocytes, Smooth Muscle / Q000276:immunology; D017510:Protein Folding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012216:Rheumatic Diseases / Q000235:genetics / Q000276:immunology / Q000503:physiopathology*; D015398:Signal Transduction / Q000276:immunology / Q000502:physiology*; D000070918:Synoviocytes / Q000378:metabolism; D056811:Unfolded Protein Response / Q000276:immunology*; D019892:eIF-2 Kinase / Q000378:metabolism
chemical_list: D051702:Activating Transcription Factor 6; D000091342:Endoplasmic Reticulum Chaperone BiP; D004722:Endoribonucleases; D015796:HLA-B27 Antigen; D006360:Heat-Shock Proteins; D017346:Protein Serine-Threonine Kinases; D019892:eIF-2 Kinase; C528229:ERN1 protein, human