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

Type 2 inflammation‒related cytokine IL-13 plays a protective role in experimental papilloma induction in mice. To understand the mechanisms by which IL-13 contributes to papilloma formation, we utilized Il13rα1-knockout (KO) mice in a widely used 7,12-dimethylbenz[a]anthracene/12-O-tetradecanoyl phorbol-13-acetate two-stage skin carcinogenesis protocol that mimics the development of squamous cell carcinoma. KO mice developed more papillomas and significantly faster than wild-type mice. Papilloma development reduced regulatory T cells in wild-type mice but substantially less in KO mice. In line with this, IL-2 and IL-10 levels decreased in wild-type mice but not in KO mice. Furthermore, systemic IL-5 and TSLP levels were elevated, whereas IL-22 was decreased during papilloma formation in the skin of KO mice. Polymorphonuclear myeloid‒derived suppressor cells were decreased in the KO mice at the early phase of papilloma induction. We show 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 through type II IL-4 receptor in tumor development.

Selective Targeting and Tissue Penetration to the Retina by a Systemically Administered Vascular Homing Peptide in Oxygen Induced Retinopathy (OIR).

Pathological angiogenesis is the hallmark of ischemic retinal diseases among them retinopathy of prematurity (ROP) and proliferative diabetic retinopathy (PDR). Oxygen-induced retinopathy (OIR) is a pure hypoxia-driven angiogenesis model and a widely used model for ischemic retinopathies. We explored whether the vascular homing peptide CAR (CARSKNKDC) which recognizes angiogenic blood vessels can be used to target the retina in OIR. We were able to demonstrate that the systemically administered CAR vascular homing peptide homed selectively to the preretinal neovessels in OIR. As a cell and tissue-penetrating peptide, CAR also penetrated into the retina. Hyperoxia used to induce OIR in the retina also causes bronchopulmonary dysplasia in the lungs. We showed that the CAR peptide is not targeted to the lungs in normal mice but is targeted to the lungs after hyperoxia-/hypoxia-treatment of the animals. The site-specific delivery of the CAR peptide to the pathologic retinal vasculature and the penetration of the retinal tissue may offer new opportunities for treating retinopathies more selectively and with less side effects.