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

Abstract The 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 lympha...

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Autores principales:	Martina Vranova, Mona C. Friess, Neda Haghayegh Jahromi, Victor Collado-Diaz, Angela Vallone, Olivia Hagedorn, Maria Jadhav, Ann-Helen Willrodt, Anna Polomska, Jean-Christophe Leroux, Steven T. Proulx, Cornelia Halin
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5f21cf0cfca3477eb75f31012925eeff
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spelling	oai:doaj.org-article:5f21cf0cfca3477eb75f31012925eeff2021-12-02T15:09:33ZOpposing roles of endothelial and leukocyte-expressed IL-7Rα in the regulation of psoriasis-like skin inflammation10.1038/s41598-019-48046-y2045-2322https://doaj.org/article/5f21cf0cfca3477eb75f31012925eeff2019-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-48046-yhttps://doaj.org/toc/2045-2322Abstract The 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.Martina VranovaMona C. FriessNeda Haghayegh JahromiVictor Collado-DiazAngela ValloneOlivia HagedornMaria JadhavAnn-Helen WillrodtAnna PolomskaJean-Christophe LerouxSteven T. ProulxCornelia HalinNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-13 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Martina Vranova Mona C. Friess Neda Haghayegh Jahromi Victor Collado-Diaz Angela Vallone Olivia Hagedorn Maria Jadhav Ann-Helen Willrodt Anna Polomska Jean-Christophe Leroux Steven T. Proulx Cornelia Halin Opposing roles of endothelial and leukocyte-expressed IL-7Rα in the regulation of psoriasis-like skin inflammation
description	Abstract The 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.
format	article
author	Martina Vranova Mona C. Friess Neda Haghayegh Jahromi Victor Collado-Diaz Angela Vallone Olivia Hagedorn Maria Jadhav Ann-Helen Willrodt Anna Polomska Jean-Christophe Leroux Steven T. Proulx Cornelia Halin
author_facet	Martina Vranova Mona C. Friess Neda Haghayegh Jahromi Victor Collado-Diaz Angela Vallone Olivia Hagedorn Maria Jadhav Ann-Helen Willrodt Anna Polomska Jean-Christophe Leroux Steven T. Proulx Cornelia Halin
author_sort	Martina Vranova
title	Opposing roles of endothelial and leukocyte-expressed IL-7Rα in the regulation of psoriasis-like skin inflammation
title_short	Opposing roles of endothelial and leukocyte-expressed IL-7Rα in the regulation of psoriasis-like skin inflammation
title_full	Opposing roles of endothelial and leukocyte-expressed IL-7Rα in the regulation of psoriasis-like skin inflammation
title_fullStr	Opposing roles of endothelial and leukocyte-expressed IL-7Rα in the regulation of psoriasis-like skin inflammation
title_full_unstemmed	Opposing roles of endothelial and leukocyte-expressed IL-7Rα in the regulation of psoriasis-like skin inflammation
title_sort	opposing roles of endothelial and leukocyte-expressed il-7rα in the regulation of psoriasis-like skin inflammation
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/5f21cf0cfca3477eb75f31012925eeff
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Opposing roles of endothelial and leukocyte-expressed IL-7Rα in the regulation of psoriasis-like skin inflammation

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