Distinct molecular signature of human skin Langerhans cells denotes critical differences in cutaneous dendritic cell immune regulation
Distinct molecular signature of human skin Langerhans cells denotes critical differences in cutaneous dendritic cell immune regulation
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.
695-703
Polak, M.E.
e0ac5e1a-7074-4776-ba23-490bd4da612d
Thirdborough, S.M.
161784fb-c8e3-4beb-86b1-cd8bc8ddf8de
Ung, C.Y.
e53a9511-f3ad-4256-8bcf-b6687d15bf57
Elliott, T.
16670fa8-c2f9-477a-91df-7c9e5b453e0e
Healy, E.
400fc04d-f81a-474a-ae25-7ff894be0ebd
Freeman, T.
4edfae3c-0dac-463b-89e2-d83c72464cce
Ardern-Jones, M.R.
7ac43c24-94ab-4d19-ba69-afaa546bec90
March 2014
Polak, M.E.
e0ac5e1a-7074-4776-ba23-490bd4da612d
Thirdborough, S.M.
161784fb-c8e3-4beb-86b1-cd8bc8ddf8de
Ung, C.Y.
e53a9511-f3ad-4256-8bcf-b6687d15bf57
Elliott, T.
16670fa8-c2f9-477a-91df-7c9e5b453e0e
Healy, E.
400fc04d-f81a-474a-ae25-7ff894be0ebd
Freeman, T.
4edfae3c-0dac-463b-89e2-d83c72464cce
Ardern-Jones, M.R.
7ac43c24-94ab-4d19-ba69-afaa546bec90
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), .
(doi:10.1038/jid.2013.375).
(PMID:24005050)
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.
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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
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Local EPrints ID: 356768
URI: http://eprints.soton.ac.uk/id/eprint/356768
ISSN: 0022-202X
PURE UUID: 0a8054b5-2eac-48dc-99ba-43fb2cabcd58
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Date deposited: 16 Sep 2013 10:45
Last modified: 15 Mar 2024 03:28
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Author:
C.Y. Ung
Author:
T. Freeman
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