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.
Keywords:
Arthritis; Autoimmunity; Cartilage; Inflammation; P2X7 receptor; Purinergic signaling; Transglutaminase.
MeSH terms
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Animals
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Arthritis, Experimental / genetics
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Arthritis, Experimental / immunology*
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Arthritis, Experimental / pathology
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Arthritis, Rheumatoid / genetics
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Arthritis, Rheumatoid / immunology*
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Arthritis, Rheumatoid / pathology
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Autoimmunity
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Bone and Bones / immunology*
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Bone and Bones / pathology
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Cartilage / immunology*
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Cartilage / pathology
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Cytokines / genetics
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Cytokines / immunology
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GTP-Binding Proteins / genetics
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GTP-Binding Proteins / immunology*
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Gene Expression Regulation
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Humans
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Immunity, Innate
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Inflammasomes / genetics
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Inflammasomes / immunology
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Inflammation
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NLR Family, Pyrin Domain-Containing 3 Protein / genetics
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NLR Family, Pyrin Domain-Containing 3 Protein / immunology
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Protein Glutamine gamma Glutamyltransferase 2
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Protein Transport / immunology
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Receptors, Purinergic P2X7 / genetics
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Receptors, Purinergic P2X7 / immunology*
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Signal Transduction
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Transglutaminases / genetics
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Transglutaminases / immunology*
Substances
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Cytokines
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Inflammasomes
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NLR Family, Pyrin Domain-Containing 3 Protein
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NLRP3 protein, human
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Receptors, Purinergic P2X7
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Protein Glutamine gamma Glutamyltransferase 2
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Transglutaminases
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GTP-Binding Proteins