title: UVB-induced melanocyte proliferation in neonatal mice driven by CCR2-independent recruitment of Ly6c(low)MHCII(hi) macrophages.
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.
authors: Queensland Institute of Medical Research, Brisbane, Queensland, Australia.
authors: Herlina Y
authors: HY
authors: Handoko
authors: Mathieu P
authors: MP
authors: Rodero
authors: Glen M
authors: GM
authors: Boyle
authors: Blake
authors: B
authors: Ferguson
authors: Christian
authors: C
authors: Engwerda
authors: Geoff
authors: G
authors: Hill
authors: H Konrad
authors: HK
authors: Muller
authors: Kiarash
authors: K
authors: Khosrotehrani
authors: Graeme J
authors: GJ
authors: Walker
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000950:Antigens, Ly / Q000378:metabolism*; D049109:Cell Proliferation / Q000528:radiation effects*; D002471:Cell Transformation, Neoplastic / Q000473:pathology; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D020381:Interleukin-17 / Q000378:metabolism; D008264:Macrophages / Q000276:immunology* / Q000473:pathology; D008544:Melanocytes / Q000378:metabolism* / Q000473:pathology / Q000528:radiation effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010641:Phenotype; D054390:Receptors, CCR2 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D012307:Risk Factors; D012867:Skin / Q000378:metabolism / Q000473:pathology; D013471:Sunburn / Q000150:complications; D013997:Time Factors; D014466:Ultraviolet Rays
chemical_list: D000950:Antigens, Ly; C515335:Ccr2 protein, mouse; D000949:Histocompatibility Antigens Class II; D020381:Interleukin-17; C494192:Ly-6C antigen, mouse; D054390:Receptors, CCR2