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: | , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
2023
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| 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 |
| Zusammenfassung: | 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. |
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| Beschreibung: | Gesehen am 08.05.2023 Published: 31 December 2022 |
| Beschreibung: | Online Resource |
| ISSN: | 2073-4409 |
| DOI: | 10.3390/cells12010172 |