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P2X7 receptor-mediated TG2 externalization: a link to inflammatory arthritis?
Daniel Aeschlimann1,2, Vera Knäuper3,4
1Matrix 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.
None:
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.
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