Opposing roles of endothelial and leukocyte-expressed IL-7R? in the regulation of psoriasis-like skin inflammation.

ABSTRACT: The interleukin 7 receptor alpha chain (IL-7R?) 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-7R? and CD132) and that IL-7 supports lymphatic drainage. This suggested that activation of IL-7R? 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-7R? 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-7R? (IL-7R??EC 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-7R? blocking antibody ameliorated inflammatory symptoms. These data identify IL-7R? 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.

SUBMITTER: Vranova M 

PROVIDER: S-EPMC6691132 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature