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

• Verfasst von: Cousin, Nikola [VerfasserIn]
• Verfasst von: Bartel, Sophie [VerfasserIn]
• Verfasst von: Scholl, Jeannette [VerfasserIn]
• Verfasst von: Tacconi, Carlotta [VerfasserIn]
• Verfasst von: Egger, Annina [VerfasserIn]
• Verfasst von: Thorhallsdottir, Gudrun [VerfasserIn]
• Verfasst von: Neri, Dario [VerfasserIn]
• Verfasst von: Dieterich, Lothar [VerfasserIn]
• Verfasst von: Detmar, Michael [VerfasserIn]
• Titel: Antibody-mediated delivery of VEGF-C promotes long-lasting lymphatic expansion that reduces recurrent inflammation
• Verf.angabe: Nikola Cousin, Sophie Bartel, Jeannette Scholl, Carlotta Tacconi, Annina Egger, Gudrun Thorhallsdottir, Dario Neri, Lothar C. Dieterich and Michael Detmar
• Jahr: 2023
• Umfang: 15 S.
• Fussnoten: Gesehen am 08.05.2023 ; Published: 31 December 2022
• Titel Quelle: Enthalten in: Cells
• Ort Quelle: Basel : MDPI, 2012
• Jahr Quelle: 2023
• Band/Heft Quelle: 12(2023), 1, Artikel-ID 172, Seite 1-15
• ISSN Quelle: 2073-4409
• DOI: doi:10.3390/cells12010172
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: dermatitis
• Sach-SW: lymphatic vessel
• Sach-SW: psoriasis
• Sach-SW: recurrence
• Sach-SW: targeted delivery
• Sach-SW: VEGF-C
• K10plus-PPN: 1844785165

Abstract

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.