Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 43, Issue 1, Pages 270-280Publisher
WILEY-BLACKWELL
DOI: 10.1002/eji.201242654
Keywords
DC; DC-SIGN; E-cadherin; Langerhans cells; Langerin
Categories
Funding
- Ministry of Education, Science, Sport, and Culture
- Ministry of Health and Labor and Welfare, Japan [22591780]
- Japanese Health Sciences Foundation
- Promotion and Mutual Aid Corporation for Private Schools of Japan
- Netherlands Organization for Scientific Research [VICI 918.10.619]
- Grants-in-Aid for Scientific Research [22591780, 25461715] Funding Source: KAKEN
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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-beta 1. 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-cadherinE-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.
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