UVB-Induced Melanocyte Proliferation in Neonatal Mice Driven by CCR2-Independent Recruitment of Ly6clowMHCIIhi Macrophages
Autor: | Mathieu P Rodero, Herlina Y. Handoko, Graeme J. Walker, Geoffrey R. Hill, Blake Ferguson, Glen M. Boyle, Christian R. Engwerda, Kiarash Khosrotehrani, H. Konrad Muller |
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Přispěvatelé: | Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques (LCBPT - UMR 8601), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Queensland Institute of Medical Research |
Rok vydání: | 2013 |
Předmět: |
CCR2
Time Factors Receptors CCR2 Ultraviolet Rays [SDV]Life Sciences [q-bio] Population Sunburn Inflammation Dermatology Biology Melanocyte Biochemistry Melanocyte migration Mice 03 medical and health sciences Chemokine receptor 0302 clinical medicine Risk Factors medicine Animals Antigens Ly Neoplastic transformation education Molecular Biology ComputingMilieux_MISCELLANEOUS Cell Proliferation Skin 030304 developmental biology Mice Knockout 0303 health sciences education.field_of_study integumentary system Macrophages Interleukin-17 Histocompatibility Antigens Class II Cell Biology Mice Inbred C57BL Cell Transformation Neoplastic Phenotype medicine.anatomical_structure Animals Newborn 030220 oncology & carcinogenesis Immunology Cancer research Melanocytes medicine.symptom Melanocyte proliferation |
Zdroj: | Journal of Investigative Dermatology Journal of Investigative Dermatology, Nature Publishing Group, 2013, 133 (7), pp.1803-1812. ⟨10.1038/JID.2013.9⟩ |
ISSN: | 0022-202X 1523-1747 |
Popis: | 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. |
Databáze: | OpenAIRE |
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