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Langerin-expressing dendritic cells in human tissues are related to CD1c+ dendritic cells and distinct from Langerhans cells and CD141high XCR1+ dendritic cells

Lookup NU author(s): Dr Venetia BigleyORCiD, Dr Naomi McGovern, Dr Paul Milne, Dr Rachel Dickinson, Sarah Pagan, Professor Muzlifah Haniffa, Professor Matthew CollinORCiD

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

Langerin is a C-type lectin expressed at high level by LCs of the epidermis. Langerin is also expressed by CD8(+)/CD103(+) XCR1(+) cross-presenting DCs of mice but is not found on the homologous human CD141(high) XCR1(+) myeloid DC. Here, we show that langerin is expressed at a low level on DCs isolated from dermis, lung, liver, and lymphoid tissue and that langerin(+) DCs are closely related to CD1c(+) myeloid DCs. They are distinguishable from LCs by the level of expression of CD1a, EpCAM, CD11b, CD11c, CD13, and CD33 and are found in tissues and tissue-draining LNs devoid of LCs. They are unrelated to CD141(high) XCR1(+) myeloid DCs, lacking the characteristic expression profile of cross-presenting DCs, conserved between mammalian species. Stem cell transplantation and DC deficiency models confirm that dermal langerin(+) DCs have an independent homeostasis to LCs. Langerin is not expressed by freshly isolated CD1c(+) blood DCs but is rapidly induced on CD1c(+) DCs by serum or TGF-beta via an ALK-3-dependent pathway. These results show that langerin is expressed outside of the LC compartment of humans and highlight a species difference: langerin is expressed by the XCR1(+) "DC1" population of mice but is restricted to the CD1c(+) "DC2" population of humans (homologous to CD11b(+) DCs in the mouse).


Publication metadata

Author(s): Bigley V, McGovern N, Milne P, Dickinson R, Pagan S, Cookson S, Haniffa M, Collin M

Publication type: Article

Publication status: Published

Journal: Journal of Leukocyte Biology

Year: 2015

Volume: 97

Issue: 4

Pages: 627-634

Print publication date: 01/04/2015

Online publication date: 16/12/2014

Acceptance date: 16/10/2014

Date deposited: 10/06/2015

ISSN (print): 0741-5400

ISSN (electronic): 1938-3673

Publisher: Federation of American Societies for Experimental Biology

URL: http://dx.doi.org/10.1189/jlb.1HI0714-351R

DOI: 10.1189/jlb.1HI0714-351R

PubMed id: 25516751


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Funding

Funder referenceFunder name
British Society for Haematology, Bright Red
George Walker Foundation
Histiocytosis Association
Histiocytosis Research Trust
Medical Research Council
WT088555MAWellcome Trust
101155/Z/13/ZWellcome Trust

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