Regular article
Epithelial and mesenchymal cell biology
Altered Dermal Fibroblasts in Systemic Sclerosis Display Podoplanin and CD90

https://doi.org/10.1016/j.ajpath.2016.06.020Get rights and content
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Tissue injury triggers the activation and differentiation of multiple cell types to minimize damage and initiate repair processes. In systemic sclerosis, these repair processes appear to run unchecked, leading to aberrant remodeling and fibrosis of the skin and multiple internal organs, yet the fundamental pathological defect remains unknown. We describe herein a transition wherein the abundant CD34+ dermal fibroblasts present in healthy human skin disappear in the skin of systemic sclerosis patients, and CD34, podoplanin+, and CD90+ fibroblasts appear. This transition is limited to the upper dermis in several inflammatory skin diseases, yet in systemic sclerosis, it can occur in all regions of the dermis. In vitro, primary dermal fibroblasts readily express podoplanin in response to the inflammatory stimuli tumor necrosis factor and IL-1β. Furthermore, we show that on acute skin injury in both human and murine settings, this transition occurs quickly, consistent with a response to inflammatory signaling. Transitioned fibroblasts partially resemble the cells that form the reticular networks in organized lymphoid tissues, potentially linking two areas of fibroblast research. These results allow for the visualization and quantification of a basic stage of fibroblast differentiation in inflammatory and fibrotic diseases in the skin.

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Supported by NIH Clinical & Translational Science Institute grant UL1-TR000157; National Institute of Arthritis and Musculoskeletal and Skin Diseases grants 5P30AR061271, 1P50AR060780, and 2R01AR051089 (R.L.); and NIH grant 5T32A1007309-27 (A.M.S.B.).

B.N. and L.M.R. contributed equally to this work.

Disclosures: BS1 antibody was provided by Biogen.