| First Author | Vranova M | Year | 2019 |
| Journal | Sci Rep | Volume | 9 |
| Issue | 1 | Pages | 11714 |
| PubMed ID | 31406267 | Mgi Jnum | J:286225 |
| Mgi Id | MGI:6387442 | Doi | 10.1038/s41598-019-48046-y |
| Citation | Vranova M, et al. (2019) Opposing roles of endothelial and leukocyte-expressed IL-7Ralpha in the regulation of psoriasis-like skin inflammation. Sci Rep 9(1):11714 |
| abstractText | The interleukin 7 receptor alpha chain (IL-7Ralpha) 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-7Ralpha and CD132) and that IL-7 supports lymphatic drainage. This suggested that activation of IL-7Ralpha 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-7Ralpha 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-7Ralpha (IL-7Ralpha(DeltaEC) 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-7Ralpha blocking antibody ameliorated inflammatory symptoms. These data identify IL-7Ralpha 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. |
