Vranova, MartinaMartinaVranovaFriess, Mona CMona CFriessHaghayegh Jahromi, NedaNedaHaghayegh JahromiCollado-Diaz, VictorVictorCollado-DiazVallone, AngelaAngelaValloneHagedorn, OliviaOliviaHagedornJadhav, MariaMariaJadhavWillrodt, Ann-HelenAnn-HelenWillrodtPolomska, AnnaAnnaPolomskaLeroux, Jean-ChristopheJean-ChristopheLerouxProulx, Steven ThomasSteven ThomasProulxHalin, CorneliaCorneliaHalin2024-10-282024-10-282019-08-12https://boris-portal.unibe.ch/handle/20.500.12422/183043The interleukin 7 receptor alpha chain (IL-7Rα) is predominately expressed by lymphocytes, and activation by its ligand IL-7 supports the development and maintenance of T cells and boosts T-cell mediated immunity. We recently reported that lymphatic endothelial cells (LECs) in dermal lymphatics also express IL-7 and its receptor chains (IL-7Rα and CD132) and that IL-7 supports lymphatic drainage. This suggested that activation of IL-7Rα signaling in lymphatics could exert inflammation-resolving activity, by promoting the clearance of excess tissue fluid. Here we investigated how the potentially opposing effects of IL-7Rα signaling in immune cells and in the lymphatic vasculature would affect the development and progression of psoriasis-like skin inflammation. We found that during acute and chronic skin inflammation mice with an endothelial-specific deletion of IL-7Rα (IL-7RαΔEC mice) developed more edema compared to control mice, as a consequence of impaired lymphatic drainage. However, systemic treatment of wild-type mice with IL-7 exacerbated edema and immune cell infiltration in spite of increasing lymphatic drainage, whereas treatment with IL-7Rα blocking antibody ameliorated inflammatory symptoms. These data identify IL-7Rα signaling as a new pathway in psoriasis-like skin inflammation and show that its pro-inflammatory effects on the immune compartment override its anti-inflammatory, drainage-enhancing effects on the endothelium.en500 - Science::570 - Life sciences; biology600 - Technology::610 - Medicine & healtharticle10.7892/boris.1346863140626710.1038/s41598-019-48046-y