Distinct molecular signature of human skin Langerhans cells denotes critical differences in cutaneous dendritic cell immune regulation


Polak, M.E., Thirdborough, S.M., Ung, C.Y., Elliott, T., Healy, E., Freeman, T. and Ardern-Jones, M.R. (2013) Distinct molecular signature of human skin Langerhans cells denotes critical differences in cutaneous dendritic cell immune regulation Journal of Investigative Dermatology, 134, (3), pp. 695-703. (doi:10.1038/jid.2013.375). (PMID:24005050).

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Description/Abstract

Langerhans cells (LCs) are professional antigen presenting cells (APCs) residing in the epidermis. Despite their high potential to activate T lymphocytes, current understanding of human LC biology is limited. Genome-wide comparison of the transcriptional profiles of human skin migratory CD1a+ LCs and CD11c+ dermal dendritic cells (DDCs) demonstrated significant differences between these ‘dendritic cell’ types, including preferential expression of 625 genes (P<0.05) in LC and 914 genes (P<0.05) in DDC. Analysis of the temporal regulation of molecular networks activated after stimulation with TNF-? confirmed the unique molecular signature of LCs. Although LCs conformed to the phenotype of professional APC, inflammatory signalling activated primarily genes associated with cellular metabolism and mitochondrial activation (e.g. CYB561, MRPS35), cell membrane re-organisation and antigen acquisition and degradation (CAV1, PSMD14) (P<0.05–P<0.0001). Conversely, TNF-? induced classical activation in DDCs with early down-regulation of surface receptors (MRC1, C-type lectins), and subsequent up-regulation of cytokines, chemokines (IL1a, IL1b, CCL18) and matrix metalloproteinases (MMP1, MMP3, MMP9), (P<0.05–P<0.0001). Functional interference of caveolin abrogated LCs superior ability to cross-present antigens to CD8+ T lymphocytes, highlighting the importance of these networks to biological function. Taken together these observations support the idea of distinct biological roles of cutaneous DC types.

Item Type: Article
Digital Object Identifier (DOI): doi:10.1038/jid.2013.375
ISSNs: 0022-202X (print)
Subjects: Q Science > QR Microbiology > QR180 Immunology
R Medicine > RL Dermatology
Organisations: Faculty of Medicine
ePrint ID: 356768
Date :
Date Event
2 August 2013Accepted/In Press
31 October 2013e-pub ahead of print
March 2014Published
Date Deposited: 16 Sep 2013 10:45
Last Modified: 17 Apr 2017 14:58
Further Information:Google Scholar
URI: http://eprints.soton.ac.uk/id/eprint/356768

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