title: Interleukin-7 is produced by afferent lymphatic vessels and supports lymphatic drainage.
abstract: The cytokine interleukin (IL)-7 exerts essential roles in lymph node (LN) organogenesis and lymphocyte development and homeostasis. Recent studies have identified lymphatic endothelial cells (LECs) as a major source of IL-7 in LNs. Here, we report that LECs not only produce IL-7, but also express the IL-7 receptor chains IL-7Rα and CD132. Stimulation with recombinant IL-7 enhanced LEC in vitro activity and induced lymphangiogenesis in the cornea of wild-type (WT) mice. Whereas in IL-7Rα(-/-) mice, dermal lymphatic vessels (LVs) were abnormally organized and lymphatic drainage was compromised, transgenic overexpression of IL-7 in mice resulted in an expanded dermal LV network with increased drainage function. Moreover, systemic treatment with recombinant IL-7 enhanced lymphatic drainage in the skin of WT mice and of mice devoid of lymphocytes. Experiments in IL-7Rα(-/-) bone marrow chimeras demonstrated that the drainage-enhancing activity of IL-7 was exclusively dependent on IL-7Rα expression in stromal but not in hematopoietic cells. Finally, near-infrared in vivo imaging performed in IL-7Rα(-/-) mice revealed that the pumping activity of collecting vessels was normal but fluid uptake into lymphatic capillaries was defective. Overall, our data point toward an unexpected new role for IL-7 as a potential autocrine mediator of lymphatic drainage.
authors: Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, ETH Zurich, Zurich, Switzerland;
authors: Maria
authors: M
authors: Iolyeva
authors: David
authors: D
authors: Aebischer
authors: Steven T
authors: ST
authors: Proulx
authors: Ann-Helen
authors: AH
authors: Willrodt
authors: Tatiana
authors: T
authors: Ecoiffier
authors: Simone
authors: S
authors: Häner
authors: Grégory
authors: G
authors: Bouchaud
authors: Carsten
authors: C
authors: Krieg
authors: Lucas
authors: L
authors: Onder
authors: Burkhard
authors: B
authors: Ludewig
authors: Laura
authors: L
authors: Santambrogio
authors: Onur
authors: O
authors: Boyman
authors: Lu
authors: L
authors: Chen
authors: Daniela
authors: D
authors: Finke
authors: Cornelia
authors: C
authors: Halin
mesh_terms: D000818:Animals; D042783:Endothelial Cells / Q000378:metabolism*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D015851:Interleukin-7 / Q000378:metabolism*; D042601:Lymphatic Vessels / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
chemical_list: C508605:IL7 protein, human; D015851:Interleukin-7; C576410:interleukin-7, mouse
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