title: IL-23 Inhibits Melanoma Development by Augmenting DNA Repair and Modulating T Cell Subpopulations.
abstract: In animal models, IL-12 and IL-23 participate in the development of malignant neoplasms of keratinocytes. However, the role of these cytokines in pigmented lesion development and their progression to melanoma has received little attention. IL-12p35, IL-23p19, and IL-12/IL-23p40 knockout mice on a C3H/HeN background, subjected to a melanomagenesis protocol, demonstrated profound differences in susceptibility to nevus initiation, transformation, tumorigenicity, and metastatic potential. IL-23 was found to be essential for melanocyte homeostasis, whereas IL-12 supported nevus development. A direct action of IL-23 on primary melanocytes, shown to be IL-23R+, demonstrated that DNA repair of damaged melanocytes requires IL-23. Furthermore, IL-23 modulated the cutaneous microenvironment by limiting regulatory T cells and IFN-γ and inhibiting IL-10 production. Neutralizing Ab to IFN-γ, but not IL-17, inhibited nevus development (p < 0.01).
authors.affiliation: Department of Dermatology, University of Alabama at Birmingham School of Medicine, Birmingham, AL 35294; and.
authors.forename: Tahseen H
authors.initials: TH
authors.lastname: Nasti
authors.affiliation: Department of Dermatology, University of Alabama at Birmingham School of Medicine, Birmingham, AL 35294; and.
authors.forename: J Barry
authors.initials: JB
authors.lastname: Cochran
authors.affiliation: Department of Dermatology, University of Alabama at Birmingham School of Medicine, Birmingham, AL 35294; and.
authors.forename: Raj V
authors.identifier: 0000-0003-3387-943X
authors.initials: RV
authors.lastname: Vachhani
authors.affiliation: Department of Dermatology, University of Alabama at Birmingham School of Medicine, Birmingham, AL 35294; and.
authors.forename: Kristopher
authors.initials: K
authors.lastname: McKay
authors.affiliation: Department of Dermatology, University of Alabama at Birmingham School of Medicine, Birmingham, AL 35294; and.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Tsuruta
authors.affiliation: Department of Dermatology, University of Alabama at Birmingham School of Medicine, Birmingham, AL 35294; and.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Athar
authors.affiliation: Department of Dermatology, University of Alabama at Birmingham School of Medicine, Birmingham, AL 35294; and timares@uab.edu celmets@uabmc.edu.
authors.forename: Laura
authors.identifier: 0000-0001-8886-8354
authors.initials: L
authors.lastname: Timares
authors.affiliation: Department of Dermatology, University of Alabama at Birmingham School of Medicine, Birmingham, AL 35294; and timares@uab.edu celmets@uabmc.edu.|Birmingham Veterans Administration Medical Center, Birmingham, AL 35233.
authors.forename: Craig A
authors.initials: CA
authors.lastname: Elmets
mesh_terms: D000818:Animals; D004260:DNA Repair / Q000276:immunology*; D004195:Disease Models, Animal; D005434:Flow Cytometry; D018664:Interleukin-12; D053759:Interleukin-23 / Q000276:immunology*; D008544:Melanocytes / Q000473:pathology; D008546:Melanoma, Experimental / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008819:Mice, Nude; D016133:Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D053759:Interleukin-23; D018664:Interleukin-12