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IL-23 Inhibits Melanoma Development by Augmenting DNA Repair and Modulating T Cell Subpopulations.

Tahseen H NastiJ Barry CochranRaj V VachhaniKristopher McKayYuko TsurutaMohammad AtharLaura TimaresCraig A Elmets
Published in: Journal of immunology (Baltimore, Md. : 1950) (2016)
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).
Keyphrases
  • dna repair
  • small cell lung cancer
  • dna damage
  • randomized controlled trial
  • stem cells
  • squamous cell carcinoma
  • immune response
  • dendritic cells
  • signaling pathway
  • intellectual disability