TY - JOUR
T1 - Distinct behavior of human Langerhans cells and inflammatory dendritic epidermal cells at tight junctions in patients with atopic dermatitis
AU - Yoshida, Kazue
AU - Kubo, Akiharu
AU - Fujita, Harumi
AU - Yokouchi, Mariko
AU - Ishii, Ken
AU - Kawasaki, Hiroshi
AU - Nomura, Toshifumi
AU - Shimizu, Hiroshi
AU - Kouyama, Keisuke
AU - Ebihara, Tamotsu
AU - Nagao, Keisuke
AU - Amagai, Masayuki
N1 - Funding Information:
Disclosure of potential conflict of interest: A. Kubo has been supported by a Research Grant from the Cosmetology Research Foundation ; the Mochida Memorial Foundation for Medical and Pharmaceutical Research; Research Grants for Life Sciences and Medicine from Keio University Medical Science Fund ; Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan ; and the “Promotion of Environmental Improvement for Independence of Young Researchers” program of the Ministry of Education, Culture, Sports, Science and Technology of Japan . M. Amagai has been supported by a Health Labour Sciences Research Grant for Research on Allergic Diseases and Immunology from the Ministry of Health, Labour and Welfare of Japan . The rest of the authors declare that they have no relevant conflicts of interest.
Funding Information:
Supported in parts by Grants-in-Aid for Scientific Research and “Promotion of Environmental Improvement for Independence of Young Researchers” program from the Ministry of Education, Culture, Sports, Science and Technology of Japan ; a Health Labour Sciences Research Grant for Research on Allergic Diseases and Immunology from the Ministry of Health, Labour and Welfare of Japan ; Research Grants for Life Sciences and Medicine from Keio University Medical Science Fund ; a Keio University Grant-in-Aid for Encouragement of Young medical Scientists; the Mochida Memorial Foundation for Medical and Pharmaceutical Research; and a Research Grant from the Cosmetology Research Foundation .
Publisher Copyright:
© 2014 American Academy of Allergy, Asthma and Immunology.
PY - 2014/10/1
Y1 - 2014/10/1
N2 - 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.
AB - 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.
KW - FceRI
KW - Langerhans cell
KW - atopic dermatitis
KW - inflammatory dendritic epidermal cell
KW - langerin
KW - stratum corneum
KW - tight junction
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U2 - 10.1016/j.jaci.2014.08.001
DO - 10.1016/j.jaci.2014.08.001
M3 - Article
C2 - 25282566
AN - SCOPUS:84908093262
VL - 134
SP - 856
EP - 864
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
SN - 0091-6749
IS - 4
ER -