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Eur J Immunol. 2013 Jan;43(1):270-80. doi: 10.1002/eji.201242654. Epub 2012 Dec 11.

E-cadherin interactions are required for Langerhans cell differentiation.

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1
Department of Microbiology and Immunology, Nippon Medical School, Tokyo, Japan.

Abstract

Human skin contains the following two distinct DC subsets: (i) Langerhans cells (LCs), expressing Langerin but not DC-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN), are predominantly localized in the epidermis; and (ii) dermal DCs, expressing DC-SIGN but not Langerin, are observed mainly in the dermis. It is not known whether localization in the epidermis provides cues for LC differentiation. Here, we show that E-cadherin expressed by epidermal keratinocytes (KCs) is crucial for differentiation of LCs. Monocytes differentiated into LC-like cells in presence of IL-4, GM-CSF, and TGF-β1. However, these LC-like cells expressed not only Langerin but also DC-SIGN. Notably, co-culturing of these LC-like cells with KCs expressing E-cadherin or recombinant E-cadherin strongly decreased expression of DC-SIGN and further induced a phenotype similar to purified epidermal LCs. Moreover, pretreatment of LC-like cells with anti-E-cadherin-specific antibody completely abolished their Langerin expression, indicating the requirement of E-cadherin-E-cadherin interactions for the differentiation into Langerin(+) cells. These findings suggest that E-cadherin expressed by KCs provide environmental cues that induce differentiation of LCs in the epidermis.

PMID:
23135957
PMCID:
PMC3565449
DOI:
10.1002/eji.201242654
[Indexed for MEDLINE]
Free PMC Article
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