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
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