Distinct behavior of human Langerhans cells and inflammatory dendritic epidermal cells at tight junctions in patients with atopic dermatitis

• Published in: Journal of allergy and clinical immunology Vol. 134; no. 4; pp. 856 - 864
• Main Authors: Yoshida, Kazue, Kubo, Akiharu, Fujita, Harumi, Yokouchi, Mariko, Ishii, Ken, Kawasaki, Hiroshi, Nomura, Toshifumi, Shimizu, Hiroshi, Kouyama, Keisuke, Ebihara, Tamotsu, Nagao, Keisuke, Amagai, Masayuki
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.10.2014; Elsevier; Elsevier Limited
• Subjects: Allergic diseases; Allergies; Allergy and Immunology; Animals; Antigen Presentation; Antigens; Antigens, CD - genetics; Antigens, CD - metabolism; Asthma; atopic dermatitis; Behavior; Biological and medical sciences; Biopsy; Cell Movement; Cells, Cultured; Dendritic Cells - immunology; Dermatitis, Atopic - complications; Dermatitis, Atopic - immunology; Epidermis - pathology; FcεRI; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Humans; Ichthyosis Vulgaris - complications; Ichthyosis Vulgaris - immunology; Immunopathology; inflammatory dendritic epidermal cell; Langerhans cell; Langerhans Cells - immunology; langerin; Lectins, C-Type - genetics; Lectins, C-Type - metabolism; Mannose-Binding Lectins - genetics; Mannose-Binding Lectins - metabolism; Medical sciences; Methods; Mice; Microscopy, Electron, Scanning; Mutation; Organ Culture Techniques; Psoriasis - complications; Psoriasis - immunology; Receptors, IgE - genetics; Receptors, IgE - metabolism; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Skin; Skin allergic diseases. Stinging insect allergies; stratum corneum; tight junction; Tight Junctions - metabolism; Tight Junctions - pathology; Tight Junctions - ultrastructure; Transcriptome; Wound healing; AD; atopic dermatitis; langerin; IV; SC; stratum corneum; Biotin-SH; 3D; ZO-1; Langerhans cell; TJ; LC; FcεRI; IDEC; inflammatory dendritic epidermal cell; tight junction; DC; Dendritic cell; Ichthyosis vulgaris; EZ-Link Sulfo-NHS-LC-Biotin; Three-dimensional; Zonula occludens 1; Human; Allergy; Immunopathology; Skin disease; Stratum corneum; FcεRI receptor; Immunoglobulin receptor; Cell junction; Inflammation; Atopy; Immunology; Antigen presenting cell; Atopic dermatitis; Tight junction; Inflammatory cell; Behavior
• ISSN: 0091-6749; 1097-6825; 1097-6825
• DOI: 10.1016/j.jaci.2014.08.001

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). 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. 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. 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. 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.