title: P2X7 receptor-mediated TG2 externalization: a link to inflammatory arthritis?
abstract: Transglutaminases have important roles in stabilizing extracellular protein assemblies in tissue repair processes but some reaction products can stimulate immune activation, leading to chronic inflammatory conditions or autoimmunity. Exacerbated disease in models of inflammatory arthritis has been ascribed to sustained extracellular enzyme activity alongside formation of select protein modifications. Here, we review the evidence, with a focus on the link between P2X7R signaling and TG2 export, a pathway that we have recently discovered which ties extracellular protein modifications into the danger signal-mediated innate immune response. These recent insights offer new opportunities for therapeutic intervention.
authors: Matrix Biology and Tissue Repair Research Unit, School of Dentistry, College of Biomedical and Life Sciences, Cardiff University, Heath Park, Cardiff, CF14 4XY, UK. AeschlimannDP@Cardiff.ac.uk.|Arthritis Research UK Biomechanics and Bioengineering Centre of Excellence, College of Biomedical and Life Sciences, Cardiff University, The Sir Martin Evans Building, Museum Avenue, Cardiff, CF10 3AX, UK. AeschlimannDP@Cardiff.ac.uk.
authors: Daniel
authors: 0000-0003-0930-7706
authors: D
authors: Aeschlimann
authors: Matrix Biology and Tissue Repair Research Unit, School of Dentistry, College of Biomedical and Life Sciences, Cardiff University, Heath Park, Cardiff, CF14 4XY, UK.|Arthritis Research UK Biomechanics and Bioengineering Centre of Excellence, College of Biomedical and Life Sciences, Cardiff University, The Sir Martin Evans Building, Museum Avenue, Cardiff, CF10 3AX, UK.
authors: Vera
authors: V
authors: Knäuper
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D015551:Autoimmunity; D001842:Bone and Bones / Q000276:immunology* / Q000473:pathology; D002356:Cartilage / Q000276:immunology* / Q000473:pathology; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D019204:GTP-Binding Proteins / Q000235:genetics / Q000276:immunology*; D005786:Gene Expression Regulation; D006801:Humans; D007113:Immunity, Innate; D058847:Inflammasomes / Q000235:genetics / Q000276:immunology; D007249:Inflammation; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000235:genetics / Q000276:immunology; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D021381:Protein Transport / Q000276:immunology; D058486:Receptors, Purinergic P2X7 / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction; D011503:Transglutaminases / Q000235:genetics / Q000276:immunology*
chemical_list: D016207:Cytokines; D058847:Inflammasomes; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D058486:Receptors, Purinergic P2X7; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins
keywords: Arthritis; Autoimmunity; Cartilage; Inflammation; P2X7 receptor; Purinergic signaling; Transglutaminase