Early Inflammatory Changes in the “Perilesional Skin” of Psoriatic Plaques: Is there Interaction between Dendritic Cells and Keratinocytes?  Mayumi Komine,

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Early Inflammatory Changes in the “Perilesional Skin” of Psoriatic Plaques: Is there Interaction between Dendritic Cells and Keratinocytes?  Mayumi Komine, Masaru Karakawa, Tomonori Takekoshi, Naoki Sakurai, Yosaku Minatani, Hiroshi Mitsui, Yayoi Tada, Hidehisa Saeki, Akihiko Asahina, Kunihiko Tamaki  Journal of Investigative Dermatology  Volume 127, Issue 8, Pages 1915-1922 (August 2007) DOI: 10.1038/sj.jid.5700799 Copyright © 2007 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 2 Cryosections of skin samples from psoriatic patients were immunohistochemically stained with anti-CD1a antibody. (a) CD1a-positive cells in the lesional epidermis of a psoriatic patient. (b) CD1a-positive cells in the perilesional epidermis. (c) CD1a-positive cells in uninvolved skin from a psoriatic patient. (d) CD1a-positive cells in distant are skin. (a–d) Bar=200μm. (e) The area positively stained with anti-CD1a antibody was selected and the ratio of positive area to the whole epidermis was calculated with the image analysis software Image Pro Plus from Planetron (Tokyo, Japan). Perilesional epidermis had a significantly higher ratio of CD1a-positive area to the lesional epidermis and distant area skin. (f) The number of CD1a-positive cells in the unit length of epidermis (per low power field) was counted. Perilesional epidermis contained significantly more CD1a-positive cells than uninvolved and distant area skin epidermis. Journal of Investigative Dermatology 2007 127, 1915-1922DOI: (10.1038/sj.jid.5700799) Copyright © 2007 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 3 Cryosections of skin samples from psoriatic patients were immunohistochemically stained with anti-CD3 antibody. (a) CD3-positive cells were densely distributed in the lesional skin of psoriatic patients. (b) Perilesional, (c) uninvolved, and (d) distant area skin contained much less CD3-positive cells compared with lesional skin. (a–d) Bar=200μm. (e) The ratio of CD3-positive area to the unit area of epidermis and papillary dermis was calculated with image analysis software. Lesional epidermis has a significantly higher ratio of CD3-positive area to the perilesional and uninvolved skin epidermis. Journal of Investigative Dermatology 2007 127, 1915-1922DOI: (10.1038/sj.jid.5700799) Copyright © 2007 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 4 Immunohistochemistry of lesional and peri-lesional skin of psoriasis patients with antibodies of various DC markers. (a) HLA-DR-positive cells in the lesional skin of a psoriatic patient. (b) HLA-DR-positive cells in the perilesional skin of a psoriatic patient. There are HLA-DR-positive DCs in the perilesional epidermis. (c) CD80-positive cells in the epidermis of lesional skin of a psoriatic patient. (d) CD80-positive cells in the perilesional skin of a psoriatic patient. (e) CD86-positive cells in the epidermis of lesional skin of a psoriatic patient. (f) CD86-positive cells in the epidermis of perilesional skin of a psoriatic patient. (g) CD11c-positive cells in the lesional skin. (h) CD11c-positive cells in the perilesional skin. There were HLA-DR-positive, CD86-positive, CD80-positive, and CD11c-positive DCs in the perilesional epidermis. (i) There were only a few BDCA2-positive cells in the mid dermis of psoriatic lesions. (j) Only a small number of BDCA2-positive cells were seen in the papillary dermis of psoriatic lesions. (a–j) Bar=100μm. Journal of Investigative Dermatology 2007 127, 1915-1922DOI: (10.1038/sj.jid.5700799) Copyright © 2007 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 5 Immunohistochemistry with anti-CD83 antibody. The number of CD83-positive cells per high power field was counted and statistically analyzed. (a) CD83-positive cells in the lesional skin. (b) CD83-positive cells in the perilesional skin. (a and b) Bar=100μm. (c) The number of CD83-positive cells in the epidermal–dermal junction of perilesional skin is significantly higher than that of distant area skin. (d) Double staining with anti-CD83 antibody and anti-Langerin antibody. Merged image shows that there are CD83-positive, Langerin-positive epidermal LCs, together with CD83-positive, Langerin-negative DCs along the dermal–epidermal junction. Bar=200μm. Journal of Investigative Dermatology 2007 127, 1915-1922DOI: (10.1038/sj.jid.5700799) Copyright © 2007 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 6 Immunohistochemistry with anti-keratin K6, anti-keratin K16, and anti-C/EBPβ antibody. (a) Keratin 6 staining of perilesional epidermis shows suprabasal staining. (b) Keratin 16 staining of perilesional epidermis shows suprabasal staining. (c) C/EBPβ staining of perilesional skin shows strong nuclear staining throughout the epidermis. (d) C/EBPβ staining of distant area skin of a psoriatic patient shows nuclear staining only in the granular layer. (a–d) Bar=200μm. Journal of Investigative Dermatology 2007 127, 1915-1922DOI: (10.1038/sj.jid.5700799) Copyright © 2007 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 1 A scheme of biopsies illustrating lesional, perilesional, uninvolved, and distant area skin taken from psoriatic patients. Journal of Investigative Dermatology 2007 127, 1915-1922DOI: (10.1038/sj.jid.5700799) Copyright © 2007 The Society for Investigative Dermatology, Inc Terms and Conditions