Antibody-mediated delivery of VEGF-C promotes long-lasting lymphatic expansion that reduces recurrent inflammation

The lymphatic vascular system plays a fundamental role in inflammation by draining interstitial fluid, immune cells, antigens, and inflammatory mediators from peripheral tissues. Site-specific delivery of the lymphangiogenic growth factor VEGF-C alleviates acute inflammation in mouse models of psori...

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Hauptverfasser: Cousin, Nikola (VerfasserIn) , Bartel, Sophie (VerfasserIn) , Scholl, Jeannette (VerfasserIn) , Tacconi, Carlotta (VerfasserIn) , Egger, Annina (VerfasserIn) , Thorhallsdottir, Gudrun (VerfasserIn) , Neri, Dario (VerfasserIn) , Dieterich, Lothar (VerfasserIn) , Detmar, Michael (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 2023
In: Cells
Year: 2023, Jahrgang: 12, Heft: 1, Pages: 1-15
ISSN:2073-4409
DOI:10.3390/cells12010172
Online-Zugang:Verlag, kostenfrei, Volltext: https://doi.org/10.3390/cells12010172
Verlag: https://www.mdpi.com/2073-4409/12/1/172
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Verfasserangaben:Nikola Cousin, Sophie Bartel, Jeannette Scholl, Carlotta Tacconi, Annina Egger, Gudrun Thorhallsdottir, Dario Neri, Lothar C. Dieterich and Michael Detmar

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245 1 0 |a Antibody-mediated delivery of VEGF-C promotes long-lasting lymphatic expansion that reduces recurrent inflammation  |c Nikola Cousin, Sophie Bartel, Jeannette Scholl, Carlotta Tacconi, Annina Egger, Gudrun Thorhallsdottir, Dario Neri, Lothar C. Dieterich and Michael Detmar 
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520 |a The lymphatic vascular system plays a fundamental role in inflammation by draining interstitial fluid, immune cells, antigens, and inflammatory mediators from peripheral tissues. Site-specific delivery of the lymphangiogenic growth factor VEGF-C alleviates acute inflammation in mouse models of psoriasis and chronic colitis by enhancing local drainage. However, it is unclear whether therapeutically induced lymphangiogenesis is transient or long-lasting and whether it might prevent relapses of inflammation. Here, we investigated the long-term effects of targeted VEGF-C delivery in a chronic dermatitis model in mice. Congruent with our previous results, intravenous injection with a VEGF-C fusion protein targeted to the EDA domain of fibronectin initially resulted in reduced inflammation. Importantly, we found that targeted VEGF-C-mediated expansion of lymphatic vessels in the skin persisted for more than 170 days, long after primary inflammation had resolved. Furthermore, the treatment markedly decreased tissue swelling upon inflammatory re-challenge at the same site. Simultaneously, infiltration of leukocytes, including CD4+ T cells, macrophages, and dendritic cells, was significantly reduced in the previously treated group. In conclusion, our data show that targeted delivery of VEGF-C leads to long-lasting lymphatic expansion and long-term protection against repeated inflammatory challenge, suggesting that it is a promising new approach for the treatment of chronic, recurrent inflammatory diseases. 
650 4 |a dermatitis 
650 4 |a lymphatic vessel 
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650 4 |a recurrence 
650 4 |a targeted delivery 
650 4 |a VEGF-C 
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