{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T14:26:52Z","timestamp":1768314412069,"version":"3.49.0"},"reference-count":46,"publisher":"Wiley","license":[{"start":{"date-parts":[[2019,12,16]],"date-time":"2019-12-16T00:00:00Z","timestamp":1576454400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004895","name":"European Social Fund","doi-asserted-by":"publisher","award":["ESF_14-BM-A55-0036"],"award-info":[{"award-number":["ESF_14-BM-A55-0036"]}],"id":[{"id":"10.13039\/501100004895","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013859","name":"DAMP foundation","doi-asserted-by":"crossref","award":["ESF_14-BM-A55-0036"],"award-info":[{"award-number":["ESF_14-BM-A55-0036"]}],"id":[{"id":"10.13039\/501100013859","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["BioMed Research International"],"published-print":{"date-parts":[[2019,12,16]]},"abstract":"<jats:p><jats:italic>Background<\/jats:italic>. Hepatic fibrosis and granuloma formation as a consequence of tissue entrapped eggs produced by female schistosomes characterize the pathology of<jats:italic>Schistosoma mansoni<\/jats:italic>infection. We have previously shown that single-sex infection with female schistosomes mitigates hepatic fibrosis after secondary infection. This was associated with an increased expression of cytotoxic T-lymphocyte-associated protein-4 (CTLA-4), known as a negative regulator of T cell activation. Based on these findings, we hypothesized that administration of agonistic CTLA-4-Ig (Belatacept) is capable to prevent and\/or treat hepatic fibrosis during schistosomiasis.<jats:italic>Methods<\/jats:italic>. Mice were infected with 50<jats:italic>S. mansoni<\/jats:italic>cercariae and CTLA-4-Ig, or appropriated control-Ig was administered for 4 weeks. Preventive treatment started 4 weeks after infection, before onset of egg production, and therapeutic treatment started 8 weeks after infection when hepatic fibrosis was already established.<jats:italic>Results<\/jats:italic>. When given early after infection, livers of CTLA-4-Ig-treated mice showed significantly reduced collagen deposition and decreased expression of profibrotic genes in comparison to controls. In addition, administration of CTLA-4-Ig suppressed the inflammatory T cell response in infected mice. If therapy was started at a later time point when fibrogenesis was initiated, CTLA-4-Ig had no impact on hepatic fibrosis.<jats:italic>Conclusion<\/jats:italic>. We could demonstrate that an early preventive administration of CTLA-4-Ig suppresses effector T cell function and therefore ameliorates liver fibrosis. CTLA-4-Ig administration after onset of egg production fails to treat hepatic fibrosis.<\/jats:p>","DOI":"10.1155\/2019\/1704238","type":"journal-article","created":{"date-parts":[[2019,12,16]],"date-time":"2019-12-16T23:30:41Z","timestamp":1576539041000},"page":"1-11","source":"Crossref","is-referenced-by-count":7,"title":["Preventive CTLA-4-Ig Treatment Reduces Hepatic Egg Load and Hepatic Fibrosis in<i>Schistosoma mansoni<\/i>-Infected Mice"],"prefix":"10.1155","volume":"2019","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3861-0635","authenticated-orcid":true,"given":"Martina","family":"Sombetzki","sequence":"first","affiliation":[{"name":"Department of Tropical Medicine, Infectious Diseases and Nephrology, University Medical Center Rostock, Rostock, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne","family":"Rabes","sequence":"additional","affiliation":[{"name":"Department of Tropical Medicine, Infectious Diseases and Nephrology, University Medical 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