Christiansen, Ailsa J; Dieterich, Lothar C; Ohs, Isabel; Bachmann, Samia B; Bianchi, Roberta; Proulx, Steven T; Hollmén, Maija; Aebischer, David; Detmar, Michael (2016). Lymphatic endothelial cells attenuate inflammation via suppression of dendritic cell maturation. OncoTarget, 7(26), pp. 39421-39435. Impact Journals LLC 10.18632/oncotarget.9820
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Vascular endothelial growth factor-C (VEGF-C)-induced lymphangiogenesis and increased tissue drainage have been reported to inhibit acute and chronic inflammation, and an activated lymphatic endothelium might mediate peripheral tolerance. Using transgenic mice overexpressing VEGF-C in the skin, we found that under inflammatory conditions, VEGF-C-mediated expansion of the cutaneous lymphatic network establishes an immune-inhibitory microenvironment characterised by increased regulatory T (Treg) cells, immature CD11c+CD11b+ dendritic cells (DCs) and CD8+ cells exhibiting decreased effector function. Strikingly, lymphatic endothelial cell (LEC)-conditioned media (CM) potently suppress DC maturation with reduced expression of MHCII, CD40, and IL-6, and increased IL-10 and CCL2 expression. We identify an imbalance in prostaglandin synthase expression after LEC activation, favoring anti-inflammatory prostacyclin synthesis. Importantly, blockade of LEC prostaglandin synthesis partially restores DC maturity. LECs also produce TGF-ß1, contributing to the immune-inhibitory microenvironment. This study identifies novel mechanisms by which the lymphatic endothelium modulates cellular immune responses to limit inflammation.
Item Type: |
Journal Article (Original Article) |
|---|---|
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: |
1949-2553 |
Publisher: |
Impact Journals LLC |
Language: |
English |
Submitter: |
Ursula Zingg-Zünd |
Date Deposited: |
21 Oct 2020 13:53 |
Last Modified: |
05 Dec 2022 15:41 |
Publisher DOI: |
10.18632/oncotarget.9820 |
PubMed ID: |
27270646 |
Uncontrolled Keywords: |
Immune response Immunity Immunology and Microbiology Section VEGF-C inflammation lymphangiogenesis |
BORIS DOI: |
10.7892/boris.147218 |
URI: |
https://boris.unibe.ch/id/eprint/147218 |
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