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Updated: Jun 25, 2026

In Vitro Differentiation of Naive CD4+ T Cells into Pathogenic Th17 Cells in Mouse
Published on: October 25, 2024
IFNgamma promotes papilloma development by up-regulating Th17-associated inflammation
Mingjie Xiao1, Chunhui Wang, Jinhua Zhang
1National Laboratory of Biomacromolecules, Chinese Academy of Sciences-University of Tokyo Joint Laboratory of Structural Virology and Immunology.
Abstract:
IFNgamma plays a crucial role in immunity against a variety of transplanted tumors and methylcholanthrene-mediated tumorigenesis in mice. However, it is not clear whether and how endogenous IFNgamma influences 7,12-dimethylbenz(a)anthracene (DMBA)-induced and 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced papilloma development. We found here that IFNgamma expression was markedly up-regulated shortly after DMBA/TPA application to the skin. Surprisingly, neutralizing IFNgamma activity in vivo did not increase but rather decreased tumor development. Furthermore, IFNgamma receptor-deficient mice were also more resistant to papilloma development than their counterparts were. IFNgamma acted mainly in the promotion stage of papilloma development by enhancing TPA-induced leukocyte infiltration and epidermal hyperproliferation. The up-regulation of tumor necrosis factor alpha, interleukin (IL)-6, and transforming growth factor beta was largely dependent on host IFNgamma responsiveness. Remarkably, up-regulation of both IL-17 expression in the skin and T helper 17 (Th17) cell number in draining lymph nodes after DMBA/TPA treatment was dependent on IFNgamma signaling. Depletion of IL-17 not only decreased the DMBA/TPA-induced inflammation and keratinocyte proliferation but also delayed papilloma development. These results show that IFNgamma, under certain conditions, may promote tumor development by enhancing a Th17-associated inflammatory reaction.
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