IL-13Rα1 Suppresses Tumor Progression in Two-stage Skin Carcinogenesis Model by Regulating Regulatory T Cells

Type 2-inflammation-related cytokine Interleukin (IL)-13 plays a protective role in experimental papilloma induction in mice. To understand mechanisms by which IL-13 contributes to papilloma formation we utilized IL-13Rα1 knockout (KO) mice in widely used DMBA/TPA two-stage skin carcinogenesis protocol that mimics the development of Squamous Cell Carcinoma (SCC). KO mice developed more papillomas and significantly faster than wild-type (WT) mice. Papilloma development reduced Tregs in WT mice, but substantially less in KO mice. In line with this, IL-2 and IL-10 levels decreased in WT mice, but not in KO mice. Furthermore, systemic IL-5 and Thymic Stromal Lymphopoietin (TSLP) levels were elevated, while IL-22 was decreased during papilloma formation in the skin of KO mice. Polymorphonuclear Myeloid-derived suppressor cells (PMN-MDSCs) were decreased in the KO mice at the early phase of papilloma induction. We demonstrate that IL-13Rα1 protects from papilloma development in chemically induced skin carcinogenesis and our results provide further insights into the protective role of functional IL-4 and IL-13 signaling via type II IL-4R in tumor development.