title: LEDGF/DFS70, a major autoantigen of atopic dermatitis, is a component of keratohyalin granules.
abstract: 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.
authors.affiliation: Department of Dermatology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Japan. kazusugi@med.nagoya-u.ac.jp
authors.forename: Kazumitsu
authors.initials: K
authors.lastname: Sugiura
authors.forename: Yoshinao
authors.initials: Y
authors.lastname: Muro
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nishizawa
authors.forename: Miyako
authors.initials: M
authors.lastname: Okamoto
authors.forename: Toshimichi
authors.initials: T
authors.lastname: Shinohara
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Tomita
authors.forename: Jiro
authors.initials: J
authors.lastname: Usukura
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000032:analysis / Q000276:immunology / Q000502:physiology*; D000328:Adult; D000368:Aged; D000918:Antibody Specificity; D001324:Autoantigens / Q000502:physiology*; D003876:Dermatitis, Atopic / Q000209:etiology / Q000276:immunology*; D000091342:Endoplasmic Reticulum Chaperone BiP; D004817:Epidermis / Q000737:chemistry; D006801:Humans; D007633:Keratins / Q000032:analysis*; D008297:Male; D021381:Protein Transport; D014157:Transcription Factors / Q000032:analysis / Q000276:immunology / Q000502:physiology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D001324:Autoantigens; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; C504649:PSIP1 protein, human; D014157:Transcription Factors; C001500:keratohyalin; D007633:Keratins