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

Iolyeva, Maria and Aebischer, David and Proulx, Steven T. and Willrodt, Ann-Helen and Ecoiffier, Tatiana and Häner, Simone and Bouchaud, Grégory and Krieg, Carsten and Onder, Lucas and Ludewig, Burkhard and Santambrogio, Laura and Boyman, Onur and Chen, Lu and Finke, Daniela and Halin, Cornelia. (2013) Interleukin-7 is produced by afferent lymphatic vessels and supports lymphatic drainage. Blood, 122 (13). pp. 2271-2281.

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Official URL: http://edoc.unibas.ch/53691/

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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.
Faculties and Departments:03 Faculty of Medicine > Bereich Kinder- und Jugendheilkunde (Klinik) > Kinder- und Jugendheilkunde (UKBB) > Molekulare Medizin in der Pädiatrie (Finke)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Kinder- und Jugendheilkunde (Klinik) > Kinder- und Jugendheilkunde (UKBB) > Molekulare Medizin in der Pädiatrie (Finke)
03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Children's Hospital > Developmental Immunology (Finke)
UniBasel Contributors:Finke, Daniela
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:American Society of Hematology
ISSN:0006-4971
e-ISSN:1528-0020
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:05 Oct 2017 10:18
Deposited On:05 Oct 2017 10:18

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