title: Altered Dermal Fibroblasts in Systemic Sclerosis Display Podoplanin and CD90.
abstract: 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.
authors: Section of Rheumatology, Boston University School of Medicine, Boston, Massachusetts.
authors: Banafsheh
authors: B
authors: Nazari
authors: Section of Rheumatology, Boston University School of Medicine, Boston, Massachusetts.
authors: Lisa M
authors: LM
authors: Rice
authors: Section of Rheumatology, Boston University School of Medicine, Boston, Massachusetts.
authors: Giuseppina
authors: G
authors: Stifano
authors: Section of Rheumatology, Boston University School of Medicine, Boston, Massachusetts; Department of Microbiology, Boston University School of Medicine, Boston, Massachusetts.
authors: Alexander M S
authors: AM
authors: Barron
authors: Section of Rheumatology, Boston University School of Medicine, Boston, Massachusetts.
authors: Yu Mei
authors: YM
authors: Wang
authors: Section of Rheumatology, Boston University School of Medicine, Boston, Massachusetts.
authors: Tess
authors: T
authors: Korndorf
authors: Department of Dermatology, Boston University School of Medicine, Boston, Massachusetts.
authors: Jungeun
authors: J
authors: Lee
authors: Department of Dermatology, Boston University School of Medicine, Boston, Massachusetts.
authors: Jag
authors: J
authors: Bhawan
authors: Section of Rheumatology, Boston University School of Medicine, Boston, Massachusetts; Division of Rheumatology and Clinical Immunology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
authors: Robert
authors: R
authors: Lafyatis
authors: Section of Rheumatology, Boston University School of Medicine, Boston, Massachusetts; Department of Microbiology, Boston University School of Medicine, Boston, Massachusetts. Electronic address: browninj@bu.edu.
authors: Jeffrey L
authors: JL
authors: Browning
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002454:Cell Differentiation; D020405:Dermis / Q000276:immunology / Q000473:pathology; D005260:Female; D005347:Fibroblasts / Q000276:immunology / Q000473:pathology; D005355:Fibrosis / Q000276:immunology / Q000473:pathology*; D006801:Humans; D053583:Interleukin-1beta / Q000276:immunology / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008875:Middle Aged; D012595:Scleroderma, Systemic / Q000276:immunology / Q000473:pathology*; D012867:Skin / Q000276:immunology / Q000473:pathology; D018800:Thy-1 Antigens / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000098853:Podoplanin
chemical_list: D053583:Interleukin-1beta; D008562:Membrane Glycoproteins; D018800:Thy-1 Antigens; D014409:Tumor Necrosis Factor-alpha; C117468:PDPN protein, human; D000098853:Podoplanin