Gottron’s papules exhibit dermal accumulation of CD44 variant 7 (CD44v7) and its binding partner osteopontin: a unique molecular signature

The accumulated mucin in non-Gottron’s dermatomyositis (DM) lesions is primarily chondroitin-4-sulfate (C4S), which is immunomodulatory in vitro. Gottron’s papules are a particularly resistant manifestation of DM that often persist after other lesions have resolved with therapy. We examined non-Gottron’s DM lesions and Gottron’s papule skin biopsies for C4S, CD44v7, a CS-binding isoform causally implicated in autoimmunity, and osteopontin, a CD44v7 ligand implicated in chronic inflammation. Gottron’s papule dermis contained more C4S and CD44v7 than non-Gottron’s lesions. Normal skin showed less CD44v7 over joints relative to Gottron’s lesions. All DM dermis had increased osteopontin compared to healthy skin. Mechanically stretching cultured fibroblasts for six hours induced CD44v7 mRNA and protein, while IFN-γ treatment induced OPN mRNA and protein. Osteopontin alone did not induce CD44v7, but stretching dermal fibroblasts in the presence of osteopontin increased THP-1 monocyte binding, which is blunted by anti-CD44v7 blocking antibody. C4S, CD44v7, and osteopontin are three molecules uniquely present in Gottron’s papules that contribute to inflammation individually and in association with one another. We propose that stretch-induced CD44v7 over joints, in concert with dysregulated osteopontin levels in the skin of DM patients, increases local inflammatory cell recruitment and contributes to the pathogenesis and resistance of Gottron’s papules.