Lymphatic endothelial cells attenuate inflammation via suppression of dendritic cell maturation.

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

[img]
Preview
Text
9820-149610-4-PB.pdf - Published Version
Available under License Creative Commons: Attribution (CC-BY).

Download (2MB) | Preview

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:

21 Oct 2020 16:01

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

Actions (login required)

Edit item Edit item
Provide Feedback