IL-23 Inhibits Melanoma Development by Augmenting DNA repair and modulating T cell subpopulations

Academic Article

Abstract

  • Copyright © 2017 by The American Association of Immunologists, Inc. 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-g and inhibiting IL-10 production. Neutralizing Ab to IFN-g, but not IL-17, inhibited nevus development (p < 0.01).
  • Published In

    Digital Object Identifier (doi)

    Pubmed Id

  • 6714539
  • Author List

  • Nasti TH; Cochran JB; Vachhani RV; McKay K; Tsuruta Y; Athar M; Timares L; Elmets CA
  • Start Page

  • 950
  • End Page

  • 961
  • Volume

  • 198
  • Issue

  • 2