Abstract
Recent GWAS have uncovered consistent genetic linkage of SSc fibrotic phenotypes with TNFAIP3, encoding the ubiquitin-editing enzyme A20. A20 has been previously implicated in negative regulation of innate immunity, and hypomorphic A20 variants are associated with autoimmunity in SLE, RA,and others.The transcription factor DREAM binds to the A20 promoter to repress expression. Unbiased transcriptome analysis of skin and lung biopsies from SSc patients showed significantly decreased A20 levels and robust anti-correlation with fibrotic TGF-beta signaling.
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