Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

CD137/TNFR9/41BB was originally described as a surface molecule present on activated T and NK cells. However, its expression is broader among leukocytes, and it is also detected on hypoxic endothelial cells and inflamed blood vessels, as well as in atherosclerotic lesions. Here, we demonstrate that lymphatic endothelial cells (LECs) up-regulate CD137 expression from undetectable baseline levels on stimulation with TNF-α, LPS, and IL-1β. CD137 cross-linking with an agonistic mAb results in NF-κB nuclear translocation, followed by up-regulation of VCAM and a 3-fold increase in the production of the chemokine CCL21. Accordingly, there is a 50% increase in CCR7-dependent migration toward conditioned medium from activated LECs on CD137 cross-linking with the agonistic mAb or the natural ligand (CD137L). Such an enhancement of cell migration is also observed with monocyte-derived dendritic cells transmigrating across CD137-activated LEC monolayers. Using explanted human dermal tissue, we found that inflamed skin contains abundant CD137(+) lymphatic vessels and that ex vivo incubation of explanted human dermis with TNF-α induces CD137 expression in lymphatic capillaries. More interestingly, treatment with CD137 agonistic antibody induces CCL21 expression and DC accumulation close to lymphatic vessels. Collectively, our results demonstrate that the inflammatory function of lymphatic vessels can be regulated by CD137.

Original publication

DOI

10.1096/fj.11-201061

Type

Journal article

Journal

FASEB journal : official publication of the Federation of American Societies for Experimental Biology

Publication Date

08/2012

Volume

26

Pages

3380 - 3392

Addresses

Department of Oncology, Centre for Applied MedicalResearch, Clínica Universidad de Navarra, University of Navarra,Pío XII, Pamplona, Spain

Keywords

Dendritic Cells, Endothelial Cells, Lymphatic Vessels, Humans, Dermatitis, Inflammation, Tumor Necrosis Factor-alpha, NF-kappa B, Vascular Cell Adhesion Molecule-1, Antibodies, Monoclonal, Cell Movement, Up-Regulation, Chemokine CCL21, Tumor Necrosis Factor Receptor Superfamily, Member 9