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Identification of a novel population of Langerin+ dendritic cells

Identification of a novel population of Langerin+ dendritic cells Langerhans cells (LCs) are antigen-presenting cells that reside in the epidermis of the skin and traffic to lymph nodes (LNs). The general role of these cells in skin immune responses is not clear because distinct models of LC depletion resulted in opposite conclusions about their role in contact hypersensitivity (CHS) responses. While comparing these models, we discovered a novel population of LCs that resides in the dermis and does not represent migrating epidermal LCs, as previously thought. Unlike epidermal LCs, dermal Langerin + dendritic cells (DCs) were radiosensitive and displayed a distinct cell surface phenotype. Dermal Langerin + DCs migrate from the skin to the LNs after inflammation and in the steady state, and represent the majority of Langerin + DCs in skin draining LNs. Both epidermal and dermal Langerin + DCs were depleted by treatment with diphtheria toxin in Lang-DTREGFP knock-in mice. In contrast, transgenic hLang-DTA mice lack epidermal LCs, but have normal numbers of dermal Langerin + DCs. CHS responses were abrogated upon depletion of both epidermal and dermal LCs, but were unaffected in the absence of only epidermal LCs. This suggests that dermal LCs can mediate CHS and provides an explanation for previous differences observed in the two-model systems. Footnotes Abbreviations used: BAC, bacterial artificial chromosome; CHS, contact hypersensitivity; DNFB, dinitrofluorobenzene; DT, diphtheria toxin; DTR, DT receptor; EGFP, enhanced GFP; LC, Langerhans cell; TRITC, tetramethylrhodamine-5-(and-6)-isothiocyanate. A. Kissenpfennig's present address is Infection and Immunity Group, Centre for Cancer Research and Cell Biology, School of Biomedical Sciences, Queens University, Belfast, Northern Ireland. Submitted: 11 September 2007 Accepted: 20 November 2007 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The Journal of Experimental Medicine Rockefeller University Press

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References (63)

Publisher
Rockefeller University Press
Copyright
Copyright © 2007, by The Rockefeller University Press
ISSN
0022-1007
eISSN
1540-9538
DOI
10.1084/jem.20071966
pmid
18086865
Publisher site
See Article on Publisher Site

Abstract

Langerhans cells (LCs) are antigen-presenting cells that reside in the epidermis of the skin and traffic to lymph nodes (LNs). The general role of these cells in skin immune responses is not clear because distinct models of LC depletion resulted in opposite conclusions about their role in contact hypersensitivity (CHS) responses. While comparing these models, we discovered a novel population of LCs that resides in the dermis and does not represent migrating epidermal LCs, as previously thought. Unlike epidermal LCs, dermal Langerin + dendritic cells (DCs) were radiosensitive and displayed a distinct cell surface phenotype. Dermal Langerin + DCs migrate from the skin to the LNs after inflammation and in the steady state, and represent the majority of Langerin + DCs in skin draining LNs. Both epidermal and dermal Langerin + DCs were depleted by treatment with diphtheria toxin in Lang-DTREGFP knock-in mice. In contrast, transgenic hLang-DTA mice lack epidermal LCs, but have normal numbers of dermal Langerin + DCs. CHS responses were abrogated upon depletion of both epidermal and dermal LCs, but were unaffected in the absence of only epidermal LCs. This suggests that dermal LCs can mediate CHS and provides an explanation for previous differences observed in the two-model systems. Footnotes Abbreviations used: BAC, bacterial artificial chromosome; CHS, contact hypersensitivity; DNFB, dinitrofluorobenzene; DT, diphtheria toxin; DTR, DT receptor; EGFP, enhanced GFP; LC, Langerhans cell; TRITC, tetramethylrhodamine-5-(and-6)-isothiocyanate. A. Kissenpfennig's present address is Infection and Immunity Group, Centre for Cancer Research and Cell Biology, School of Biomedical Sciences, Queens University, Belfast, Northern Ireland. Submitted: 11 September 2007 Accepted: 20 November 2007

Journal

The Journal of Experimental MedicineRockefeller University Press

Published: Dec 24, 2007

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