Iolyeva, Maria; Aebischer, David; Proulx, Steven T; Willrodt, Ann-Helen; Ecoiffier, Tatiana; Häner, Simone; Bouchaud, Grégory; Krieg, Carsten; Onder, Lucas; Ludewig, Burkhard; Santambrogio, Laura; Boyman, Onur; Chen, Lu; Finke, Daniela; Halin, Cornelia (2013). Interleukin-7 is produced by afferent lymphatic vessels and supports lymphatic drainage. Blood, 122(13), pp. 2271-2281. American Society of Hematology 10.1182/blood-2013-01-478073
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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.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
04 Faculty of Medicine > Pre-clinic Human Medicine > Theodor Kocher Institute |
UniBE Contributor: |
Proulx, Steven Thomas |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
0006-4971 |
Publisher: |
American Society of Hematology |
Language: |
English |
Submitter: |
Ursula Zingg-Zünd |
Date Deposited: |
23 Oct 2020 10:02 |
Last Modified: |
05 Dec 2022 15:41 |
Publisher DOI: |
10.1182/blood-2013-01-478073 |
PubMed ID: |
23963040 |
BORIS DOI: |
10.7892/boris.147276 |
URI: |
https://boris.unibe.ch/id/eprint/147276 |