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LEDGF/DFS70, a major autoantigen of atopic dermatitis, is a component of keratohyalin granules.
Sugiura, Kazumitsu; Muro, Yoshinao; Nishizawa, Yuji; Okamoto, Miyako; Shinohara, Toshimichi; Tomita, Yasushi; Usukura, Jiro.
Affiliation
  • Sugiura K; Department of Dermatology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Japan. kazusugi@med.nagoya-u.ac.jp
J Invest Dermatol ; 127(1): 75-80, 2007 Jan.
Article in En | MEDLINE | ID: mdl-16858421
Lens epithelium-derived growth factor/dense fine speckles 70 kDa protein (LEDGF/DFS70) is a transcriptional cofactor, a transcriptional activator, survival factor, and HIV-1 transporter. It is also a major autoantigen in patients with atopic dermatitis (AD), because autoantibodies to this protein are found in approximately 30% of AD patients. To better understand the role of autoantibodies and autoantigens in the pathogenesis of AD, we examined the distribution of LEDGF/DFS70 in the epidermis of normal human skin by light and electron microscopic immunocytochemistry. Increased amounts of LEDGF/DFS70 were located in the nuclei of cells in the basal layer, whereas the cytoplasm of cells in the granular layer stained for LEDGF/DFS70 by light microscopy. Using immunoelectron microscopy, we observed the accumulation of LEDGF/DFS70 in keratohyalin granules (KGs) in the cytoplasm of cells in the granular layer. In addition, Ig heavy chain-binding protein/glucose-regulated protein, 78-kDa (Bip/GRP78), a stress sensing protein in the endoplasmic reticulum, colocalized with LEDGF/DFS70 in the KGs. These results suggest that LEDGF/DFS70 is predominantly located in the nucleus of the basal epidermal cells and translocates into the cytoplasm during differentiation. Once in the cytoplasm, LEDGF/DFS70 accumulates in the KGs in the granular layer. Finally, LEDGF/DFS70, a "nuclear" autoantigen in AD, may play a functional role in the KGs.
Subject(s)
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Collection: 01-internacional Database: MEDLINE Main subject: Autoantigens / Transcription Factors / Adaptor Proteins, Signal Transducing / Dermatitis, Atopic / Keratins Type of study: Etiology_studies Limits: Adult / Aged / Humans / Male Language: En Journal: J Invest Dermatol Year: 2007 Document type: Article Affiliation country: Japan Country of publication: United States
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Collection: 01-internacional Database: MEDLINE Main subject: Autoantigens / Transcription Factors / Adaptor Proteins, Signal Transducing / Dermatitis, Atopic / Keratins Type of study: Etiology_studies Limits: Adult / Aged / Humans / Male Language: En Journal: J Invest Dermatol Year: 2007 Document type: Article Affiliation country: Japan Country of publication: United States