LEDGF/DFS70, a major autoantigen of atopic dermatitis, is a component of keratohyalin granules

Kazumitsu Sugiura, Yoshinao Muro, Yuji Nishizawa, Miyako Okamoto, Toshimichi Shinohara, Yasushi Tomita, Jiro Usukura

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)75-80
Number of pages6
JournalJournal of Investigative Dermatology
Volume127
Issue number1
DOIs
Publication statusPublished - 27-01-2007

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Autoantigens
Atopic Dermatitis
Speckle
Proteins
Cytoplasm
Autoantibodies
lens epithelium-derived growth factor
keratohyalin
Light
Immunoelectron Microscopy
Nuclear Proteins
Heat-Shock Proteins
Basal Ganglia
Cell Nucleus
Epidermis
Endoplasmic Reticulum
HIV-1
Microscopy
Immunohistochemistry
Optical microscopy

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

Cite this

Sugiura, Kazumitsu ; Muro, Yoshinao ; Nishizawa, Yuji ; Okamoto, Miyako ; Shinohara, Toshimichi ; Tomita, Yasushi ; Usukura, Jiro. / LEDGF/DFS70, a major autoantigen of atopic dermatitis, is a component of keratohyalin granules. In: Journal of Investigative Dermatology. 2007 ; Vol. 127, No. 1. pp. 75-80.
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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.",
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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.

In: Journal of Investigative Dermatology, Vol. 127, No. 1, 27.01.2007, p. 75-80.

Research output: Contribution to journalArticle

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T1 - LEDGF/DFS70, a major autoantigen of atopic dermatitis, is a component of keratohyalin granules

AU - Sugiura, Kazumitsu

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