Interleukin-7 is produced by afferent lymphatic vessels and supports lymphatic drainage

Maria Iolyeva, David Aebischer, Steven T. Proulx, Ann Helen Willrodt, Tatiana Ecoiffier, Simone Häner, Grégory Bouchaud, Carsten Krieg, Lucas Onder, Burkhard Ludewig, Laura Santambrogio, Onur Boyman, Lu Chen, Daniela Finke, Cornelia Halin

Research output: Contribution to journalArticle

39 Scopus citations

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 amajor source of IL-7 inLNs. Here,wereport 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.

Original languageEnglish (US)
Pages (from-to)2271-2281
Number of pages11
JournalBlood
Volume122
Issue number13
DOIs
StatePublished - Jan 1 2013

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Iolyeva, M., Aebischer, D., Proulx, S. T., Willrodt, A. H., Ecoiffier, T., Häner, S., Bouchaud, G., Krieg, C., Onder, L., Ludewig, B., Santambrogio, L., Boyman, O., Chen, L., Finke, D., & Halin, C. (2013). Interleukin-7 is produced by afferent lymphatic vessels and supports lymphatic drainage. Blood, 122(13), 2271-2281. https://doi.org/10.1182/blood-2013-01-478073