{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T16:20:19Z","timestamp":1777998019492,"version":"3.51.4"},"reference-count":39,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,12,31]],"date-time":"2022-12-31T00:00:00Z","timestamp":1672444800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"publisher","award":["310030B_185392"],"award-info":[{"award-number":["310030B_185392"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"publisher","award":["LYVICAM"],"award-info":[{"award-number":["LYVICAM"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"publisher","award":["SKINTEGRITY:CH"],"award-info":[{"award-number":["SKINTEGRITY:CH"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"name":"European Research Council","award":["310030B_185392"],"award-info":[{"award-number":["310030B_185392"]}]},{"name":"European Research Council","award":["LYVICAM"],"award-info":[{"award-number":["LYVICAM"]}]},{"name":"European Research Council","award":["SKINTEGRITY:CH"],"award-info":[{"award-number":["SKINTEGRITY:CH"]}]},{"DOI":"10.13039\/501100003006","name":"ETH Zurich","doi-asserted-by":"publisher","award":["310030B_185392"],"award-info":[{"award-number":["310030B_185392"]}],"id":[{"id":"10.13039\/501100003006","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003006","name":"ETH Zurich","doi-asserted-by":"publisher","award":["LYVICAM"],"award-info":[{"award-number":["LYVICAM"]}],"id":[{"id":"10.13039\/501100003006","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003006","name":"ETH Zurich","doi-asserted-by":"publisher","award":["SKINTEGRITY:CH"],"award-info":[{"award-number":["SKINTEGRITY:CH"]}],"id":[{"id":"10.13039\/501100003006","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/cells12010172","type":"journal-article","created":{"date-parts":[[2023,1,2]],"date-time":"2023-01-02T02:23:06Z","timestamp":1672626186000},"page":"172","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Antibody-Mediated Delivery of VEGF-C Promotes Long-Lasting Lymphatic Expansion That Reduces Recurrent Inflammation"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1237-1429","authenticated-orcid":false,"given":"Nikola","family":"Cousin","sequence":"first","affiliation":[{"name":"Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology (ETH) Zurich, 8093 Zurich, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sophie","family":"Bartel","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology (ETH) Zurich, 8093 Zurich, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeannette","family":"Scholl","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology (ETH) Zurich, 8093 Zurich, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6431-7555","authenticated-orcid":false,"given":"Carlotta","family":"Tacconi","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology (ETH) Zurich, 8093 Zurich, Switzerland"},{"name":"Department of Biosciences, University of Milan, 20133 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annina","family":"Egger","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology (ETH) Zurich, 8093 Zurich, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gudrun","family":"Thorhallsdottir","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology (ETH) Zurich, 8093 Zurich, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dario","family":"Neri","sequence":"additional","affiliation":[{"name":"Philochem AG, 8112 Otelfingen, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7908-5710","authenticated-orcid":false,"given":"Lothar C.","family":"Dieterich","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology (ETH) Zurich, 8093 Zurich, Switzerland"},{"name":"European Center for Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5351-5054","authenticated-orcid":false,"given":"Michael","family":"Detmar","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology (ETH) Zurich, 8093 Zurich, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1089\/lrb.2008.1008","article-title":"The lymphatic system in health and disease","volume":"6","author":"Cueni","year":"2008","journal-title":"Lymphat. 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Data"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/1\/172\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:49:04Z","timestamp":1760147344000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/1\/172"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,31]]},"references-count":39,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,1]]}},"alternative-id":["cells12010172"],"URL":"https:\/\/doi.org\/10.3390\/cells12010172","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,31]]}}}