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UVB-induced melanocyte proliferation in neonatal mice driven by CCR2-independent recruitment of Ly6clow MHCIIhi macrophages

Citation

Handoko, HY and Rodero, MP and Boyle, GM and Ferguson, B and Engwerda, C and Hill, G and Muller, HK and Khosrotehrani, K and Walker, GJ, UVB-induced melanocyte proliferation in neonatal mice driven by CCR2-independent recruitment of Ly6clow MHCIIhi macrophages, Journal of Investigative Dermatology, 133, (7) pp. 1803-1812. ISSN 0022-202X (2013) [Refereed Article]

Copyright Statement

Copyright 2013 The Society for Investigative Dermatology

DOI: doi:10.1038/jid.2013.9

Abstract

Intermittent sunburns, particularly in childhood, are the strongest environmental risk factor for malignant melanoma (MM). In mice, a single neonatal UVR exposure induces MM, whereas chronic doses to adult mice do not. Neonatal UVR alters melanocyte migration dynamics by inducing their movement upward out of hair follicles into the epidermis. UVR is known to induce inflammation and recruitment of macrophages into the skin. In this study, we have used a liposomal clodronate strategy to deplete macrophages at the time of neonatal UVR, and have shown functionally that this reduces the melanocyte proliferative response. This effect was not reproduced by depletion of CD11c-expressing populations of dendritic cells. On the basis of epidermal expression array data at various time points after UVR, we selected mouse strains defective in various aspects of macrophage recruitment, activation, and effector functions, and measured their melanocyte UVR response. We identified Ly6c low MHCII hi macrophages as the major population promoting the melanocyte response across multiple strains. The activity of this subpopulation was CCR2 (C-C chemokine receptor type 2) independent and partly IL-17 dependent. By helping induce this effect, the infiltration of specific macrophage subpopulations after sunburn may be a factor in increasing the risk of subsequent neoplastic transformation of melanocytes. © 2013 The Society for Investigative Dermatology.

Item Details

Item Type:Refereed Article
Research Division:Medical and Health Sciences
Research Group:Oncology and Carcinogenesis
Research Field:Cancer Cell Biology
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Skin and Related Disorders
Author:Muller, HK (Professor Konrad Muller)
ID Code:88735
Year Published:2013
Web of Science® Times Cited:12
Deposited By:Medicine (Discipline)
Deposited On:2014-02-13
Last Modified:2017-11-06
Downloads:0

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