Antibody-Mediated Delivery of VEGF-C Promotes Long-Lasting Lymphatic Expansion That Reduces Recurrent Inflammation
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Date
2023
Publication Type
Journal Article
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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.
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published
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Journal / series
Volume
12 (1)
Pages / Article No.
172
Publisher
MDPI
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Subject
lymphatic vessel; VEGF-C; targeted delivery; dermatitis; psoriasis; recurrence
Organisational unit
03683 - Detmar, Michael (emeritus) / Detmar, Michael (emeritus)
Notes
Funding
185392 - Role of lymphatic vessels in cancer progression (SNF)