Kazue Yoshida1, Akiharu Kubo2, Harumi Fujita3, Mariko Yokouchi4, Ken Ishii5, Hiroshi Kawasaki4, Toshifumi Nomura6, Hiroshi Shimizu6, Keisuke Kouyama7, Tamotsu Ebihara4, Keisuke Nagao4, Masayuki Amagai8. 1. Department of Dermatology, Keio University School of Medicine, Tokyo, Japan; Department of Dermatology, National Center for Child Health and Development, Tokyo, Japan. 2. Department of Dermatology, Keio University School of Medicine, Tokyo, Japan; Keio-Maruho Laboratory of Skin Barriology, Keio University School of Medicine, Tokyo, Japan. Electronic address: akiharu@a5.keio.jp. 3. Department of Dermatology, Keio University School of Medicine, Tokyo, Japan; KOSÉ Endowed Program for Skin Care and Allergy Prevention, Keio University School of Medicine, Tokyo, Japan. 4. Department of Dermatology, Keio University School of Medicine, Tokyo, Japan. 5. Department of Dermatology, Keio University School of Medicine, Tokyo, Japan; Department of Dermatology, Toho University School of Medicine, Tokyo, Japan. 6. Department of Dermatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan. 7. Center for Clinical Research, Keio University School of Medicine, Tokyo, Japan. 8. Department of Dermatology, Keio University School of Medicine, Tokyo, Japan; Keio-Maruho Laboratory of Skin Barriology, Keio University School of Medicine, Tokyo, Japan; KOSÉ Endowed Program for Skin Care and Allergy Prevention, Keio University School of Medicine, Tokyo, Japan.
Abstract
BACKGROUND: The stratum corneum and tight junctions (TJs) form physical barriers in the epidermis. Dendrites of activated Langerhans cells (LCs) extend beyond the TJs to capture external antigens in mice. LCs and inflammatory dendritic epidermal cells (IDECs) are observed in the skin of patients with atopic dermatitis (AD). OBJECTIVE: We sought to investigate the characteristics of LCs and IDECs and the distribution of their antigen capture receptors in relation to TJs in normal and AD skin. METHODS: We characterized the interactions of LCs and IDECs with TJs and the expression patterns of langerin and FcεRI by using whole-mount epidermal sheets from healthy subjects and patients with AD, ichthyosis vulgaris, and psoriasis vulgaris. RESULTS: As in mouse skin, activated LCs penetrate TJs in human skin. The number of LCs with TJ penetration increased approximately 5-fold in erythematous lesional skin of patients with AD but not in nonlesional skin of patients with AD or lesions of patients with ichthyosis vulgaris or psoriasis. In contrast, IDECs localized in the lower part of the epidermis, and their dendrites extended horizontally without penetration through TJs. Although langerin accumulated on the tips of dendrites of activated LCs, FcεRI was expressed diffusely on the cell surfaces on LCs and IDECs in lesional skin from patients with AD. CONCLUSIONS: These findings highlight interesting differences between LCs and IDECs in epidermis of patients with AD, where LCs, but not IDECs, extend dendrites through the TJs, likely to capture antigens from outside the TJ barrier with a polarized distribution of langerin but not FcεRI. These behavioral differences between skin dendritic cells might reflect an important pathophysiology of AD.
BACKGROUND: The stratum corneum and tight junctions (TJs) form physical barriers in the epidermis. Dendrites of activated Langerhans cells (LCs) extend beyond the TJs to capture external antigens in mice. LCs and inflammatory dendritic epidermal cells (IDECs) are observed in the skin of patients with atopic dermatitis (AD). OBJECTIVE: We sought to investigate the characteristics of LCs and IDECs and the distribution of their antigen capture receptors in relation to TJs in normal and AD skin. METHODS: We characterized the interactions of LCs and IDECs with TJs and the expression patterns of langerin and FcεRI by using whole-mount epidermal sheets from healthy subjects and patients with AD, ichthyosis vulgaris, and psoriasis vulgaris. RESULTS: As in mouse skin, activated LCs penetrate TJs in human skin. The number of LCs with TJ penetration increased approximately 5-fold in erythematous lesional skin of patients with AD but not in nonlesional skin of patients with AD or lesions of patients with ichthyosis vulgaris or psoriasis. In contrast, IDECs localized in the lower part of the epidermis, and their dendrites extended horizontally without penetration through TJs. Although langerin accumulated on the tips of dendrites of activated LCs, FcεRI was expressed diffusely on the cell surfaces on LCs and IDECs in lesional skin from patients with AD. CONCLUSIONS: These findings highlight interesting differences between LCs and IDECs in epidermis of patients with AD, where LCs, but not IDECs, extend dendrites through the TJs, likely to capture antigens from outside the TJ barrier with a polarized distribution of langerin but not FcεRI. These behavioral differences between skin dendritic cells might reflect an important pathophysiology of AD.
Authors: Wendy F Davidson; Donald Y M Leung; Lisa A Beck; Cecilia M Berin; Mark Boguniewicz; William W Busse; Talal A Chatila; Raif S Geha; James E Gern; Emma Guttman-Yassky; Alan D Irvine; Brian S Kim; Heidi H Kong; Gideon Lack; Kari C Nadeau; Julie Schwaninger; Angela Simpson; Eric L Simpson; Jonathan M Spergel; Alkis Togias; Ulrich Wahn; Robert A Wood; Judith A Woodfolk; Steven F Ziegler; Marshall Plaut Journal: J Allergy Clin Immunol Date: 2019-01-09 Impact factor: 10.793
Authors: Nathan Dyjack; Elena Goleva; Cydney Rios; Byung Eui Kim; Lianghua Bin; Patricia Taylor; Caroline Bronchick; Clifton F Hall; Brittany N Richers; Max A Seibold; Donald Y M Leung Journal: J Allergy Clin Immunol Date: 2018-01-06 Impact factor: 10.793
Authors: Teruaki Nakatsuji; Tiffany H Chen; Aimee M Two; Kimberly A Chun; Saisindhu Narala; Raif S Geha; Tissa R Hata; Richard L Gallo Journal: J Invest Dermatol Date: 2016-07-02 Impact factor: 8.551