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

Record type: Article

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.

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Polak, M.E., Thirdborough, S.M., Ung, C.Y., Elliott, T., Healy, E., Freeman, T. and Ardern-Jones, M.R. (2014) 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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Accepted/In Press date: 2 August 2013
e-pub ahead of print date: 31 October 2013
Published date: March 2014
Organisations: Faculty of Medicine


Local EPrints ID: 356768
ISSN: 0022-202X
PURE UUID: 0a8054b5-2eac-48dc-99ba-43fb2cabcd58
ORCID for T. Elliott: ORCID iD

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Date deposited: 16 Sep 2013 10:45
Last modified: 24 Jul 2017 16:39

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Author: M.E. Polak
Author: C.Y. Ung
Author: T. Elliott ORCID iD
Author: E. Healy
Author: T. Freeman

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