Go to The Journal of Clinical Investigation
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Immunology
    • Metabolism
    • Nephrology
    • Oncology
    • Pulmonology
    • All ...
  • Videos
  • Collections
    • Resource and Technical Advances
    • Clinical Medicine
    • Reviews
    • Editorials
    • Perspectives
    • Top read articles
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • In-Press Preview
  • Concise Communication
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
Antibody-mediated delivery of VEGF-C potently reduces chronic skin inflammation
Simon Schwager, … , Dario Neri, Michael Detmar
Simon Schwager, … , Dario Neri, Michael Detmar
Published December 6, 2018
Citation Information: JCI Insight. 2018;3(23):e124850. https://doi.org/10.1172/jci.insight.124850.
View: Text | PDF
Research Article Dermatology Therapeutics

Antibody-mediated delivery of VEGF-C potently reduces chronic skin inflammation

  • Text
  • PDF
Abstract

VEGF-C is an important mediator of lymphangiogenesis and has been shown to alleviate chronic inflammation in a variety of disease models. In this study, we investigated whether targeted delivery of VEGF-C to sites of inflammation and site-specific activation of lymphatic vessels would represent a clinically feasible strategy for treating chronic skin inflammation. To this end, we generated a fusion protein consisting of human VEGF-C fused to the F8 antibody (F8-VEGF-C), which is specific for the alternatively spliced, angiogenesis-marking extradomain A (EDA) of fibronectin. In two mouse models of psoriasis-like skin inflammation, mediated by transgenic VEGF-A overexpression or repeated application of imiquimod, intravenous treatment with F8-VEGF-C but not with untargeted VEGF-C significantly reduced ear skin edema and was as effective as the clinically used TNF-α receptor-Fc fusion protein (TNFR-Fc). Treatment with F8-VEGF-C led to a marked expansion of lymphatic vessels in the inflamed skin and significantly improved lymphatic drainage function. At the same time, treatment with F8-VEGF-C significantly reduced leukocyte numbers, including CD4+ and γδ T cells. In sum, our results reveal that targeted delivery of VEGF-C and site-specific induction of lymphatic vessels represent a potentially new and promising approach for the treatment of chronic inflammatory diseases.

Authors

Simon Schwager, Silvana Renner, Teresa Hemmerle, Sinem Karaman, Steven T. Proulx, Roman Fetz, Alexandra Michaela Golding-Ochsenbein, Philipp Probst, Cornelia Halin, Dario Neri, Michael Detmar

×

Figure 2

EDA is expressed in human psoriatic lesions and inflamed skin of K14-VEGF-A mice but not in healthy skin, and F8 fusion proteins accumulate in inflamed ear skin.

Options: View larger image (or click on image) Download as PowerPoint
EDA is expressed in human psoriatic lesions and inflamed skin of K14-VEG...
(A) Immunofluorescence stainings for EDA (red) and VE-cadherin (green) in healthy and psoriatic human skin. White boxes highlight enlarged region. Scale bar: 100 μm (overview); 50 μm (merge). (B) Immunofluorescence stainings for EDA (red) and CD31 (green) in uninflamed and inflamed ear skin of K14-VEGF-A mice 21 days after challenge. Scale bar: 100 μm. (C) Quantitative biodistribution studies of radioiodinated F8-VEGF-C and F8-VEGF-C156Ser in mice with uninflamed or inflamed ears, expressed as a percentage of injected dose per gram of tissue (n = 3–5 mice per group, data represent mean ± SD). (D) Autoradiography of F8-VEGF-C and F8-VEGF-C156Ser comparing accumulation in inflamed compared with uninflamed ears (n = 4 mice per group). ID, injected dose. Arrows indicate EDA– vessels; arrowheads indicate EDA+ vessels.

Copyright © 2023 American Society for Clinical Investigation
ISSN 2379-3708

Sign up for email alerts