Abstract
Mice bearing carcinogen-induced premalignant oral lesions were previously shown to have a pro-inflammatory phenotype, which is replaced with an immune inhibitory phenotype as lesions progress to cancer. Since Th17 cells are prominent at the premalignant lesion state and their levels are supported by IL-23, studies used mice that were IL-23 receptor deficient (IL-23R KO) to determine the requirement for IL-23 signaling in the immunological and clinical status of mice with premalignant oral lesions. The results showed a dependence on IL-23 signaling for the pro-inflammatory state of mice with oral lesions as levels of IL-2, IFN-γ, IL-6, IL-17 and TNF-α were elevated in wildtype mice with premalignant oral lesions, but not in IL-23R KO mice. In contrast, as lesions progressed to cancer, the pro-inflammatory phenotype subsided and was replaced with the inhibitory mediator IL-10 and with Treg cells in wildtype mice, although not in IL-23R KO mice. Clinically, early progression of premalignant oral lesions to cancer was enhanced in IL-23R KO mice compared to progression in wildtype mice. These results show the importance of IL-23 signaling in both the pro-inflammatory phenotype characteristic of premalignant oral lesions and the inhibitory phenotype as lesions progress to cancer.