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

Kazue Yoshida, Akiharu Kubo, Harumi Fujita, Mariko Yokouchi, Ken Ishii, Hiroshi Kawasaki, Toshifumi Nomura, Hiroshi Shimizu, Keisuke Koyama, Tamotsu Ebihara, Keisuke Nagao, Masayuki Amagai

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59 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)856-864
Number of pages9
JournalJournal of Allergy and Clinical Immunology
Volume134
Issue number4
DOIs
Publication statusPublished - 2014 Oct 1

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Keywords

  • atopic dermatitis
  • FceRI
  • inflammatory dendritic epidermal cell
  • Langerhans cell
  • langerin
  • stratum corneum
  • tight junction

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Medicine(all)

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