{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T23:01:18Z","timestamp":1792450878130,"version":"4.5.0"},"reference-count":45,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2020,9,14]],"date-time":"2020-09-14T00:00:00Z","timestamp":1600041600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005624","name":"Medizinischen Hochschule Hannover","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005624","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009950","name":"Ministry of Education","doi-asserted-by":"publisher","award":["01EO1302"],"award-info":[{"award-number":["01EO1302"]}],"id":[{"id":"10.13039\/100009950","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2020,12]]},"abstract":"Abstract<\/jats:title>Background & Aims<\/jats:title>Recent evidence suggests that Interleukin (IL)\u201017\u2010producing gamma delta () T cells are the dominant pathogenic cellular component in designated autoimmune or inflammatory diseases, including biliary atresia (BA). We have previously demonstrated that retinoids effectively suppress T\u2010helper cell (Th) 17 differentiation.<\/jats:p><\/jats:sec>Methods<\/jats:title>Here, we established an in vitro system, enabling investigations of the effect of AM80 on the IL\u201017 production of T cells. Additionally, we tested the therapeutic effect of AM80 in the Rotavirus\u2010induced mouse model of BA. Co\u2010incubation of T cells with IL\u201023 and anti\u2010CD28 mAb proved most effective in inducing an IL\u201017 response in vitro. The effect of AM80 on human CCR6+CD26+ V2 cells was assessed by flow cytometry.<\/jats:p><\/jats:sec>Results<\/jats:title>AM80 efficiently reduced IL\u201017 production by murine T cells and the expression of the master transcription factor Retinoid\u2010Orphan\u2010Receptor\u2010t (ROR) in a dose\u2010dependent manner. The fraction of human CCR6+CD26+ V2 cells was significantly reduced by co\u2010incubation with AM80. Moreover, AM80 also inhibited IL\u201017 production by liver\u2010infiltrating T cells isolated from animals suffering from BA. Intraperitoneal treatment with AM80 ameliorated BA\u2010associated inflammation. However, AM80 treatment was not sufficient to control disease progression in the murine model, despite reduced inflammatory activity in the animals.<\/jats:p><\/jats:sec>Conclusions<\/jats:title>Retinoids are very efficient in down\u2010regulating IL\u201017 production by T cells in vitro and, to a lesser extent, in the BA mouse model. However, retinoids do not suffice for the control of disease progression. Thus, our data suggest that IL\u201017 is not the only factor contributing to the pathogenesis of BA.<\/jats:p><\/jats:sec>Lay summary<\/jats:title>Biliary atresia (BA) is a rare disease which affects infants, causing progressive liver failure in most children, and is the most common indication for paediatric liver transplantation. We have previously demonstrated that IL\u201017, produced by T cells, contributes to hepatic inflammation in the murine model of BA and is increased in the livers of infants suffering from the disease. In the study at hand, we demonstrate that treatment with AM80, a synthetic retinoid with superior pharmacological properties, effectively inhibits the IL\u201017 production of gamma delta T cells without generating systemic immunosuppression. Although all\u2010trans retinoic acid (ATRA) has been demonstrated to suppress differentiation of IL\u201017\u2010producing conventional T\u2010helper cells (Th17) in vitro, the therapeutic application of ATRA in vivo is limited by the compound's potential side effects caused by its instability and lack of receptor specificity. Our study is the first to show that AM80 suppresses the IL\u201017 production of T cells in a very efficient manner and that hepatic inflammation is ameliorated in mice suffering from BA. However, AM80 treatment does not suffice to block the disease progression. We conclude that factors other than IL\u201017 drive the progressive inflammation in BA. The addition of retinoids to the treatment regime of children suffering from BA might decrease the disease burden; however, further research is needed to clarify the pathomechanism and possible therapeutic interventions in humans.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.14639","type":"journal-article","created":{"date-parts":[[2020,8,20]],"date-time":"2020-08-20T15:33:41Z","timestamp":1597937621000},"page":"3031-3041","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Synthetic retinoid AM80 inhibits IL\u201017 production of gamma delta T cells and ameliorates biliary atresia in mice"],"prefix":"10.1111","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9102-124X","authenticated-orcid":false,"given":"Nora","family":"M\u00f6hn","sequence":"first","affiliation":[{"name":"Department of Pediatric Surgery Hannover Medical School Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Bruni","sequence":"additional","affiliation":[{"name":"Institute of Immunology Hannover Medical School Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1552-6163","authenticated-orcid":false,"given":"Arne","family":"Schr\u00f6der","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery Hannover Medical School Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Fr\u00f6mmel","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery Hannover Medical School Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faikah","family":"Gueler","sequence":"additional","affiliation":[{"name":"Department of Nephrology Hannover Medical School Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gertrud","family":"Vieten","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery Hannover Medical School Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Immo","family":"Prinz","sequence":"additional","affiliation":[{"name":"Institute of Immunology Hannover Medical School Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joachim F.","family":"Kuebler","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery Hannover Medical School Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claus","family":"Petersen","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery Hannover Medical School Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5639-8690","authenticated-orcid":false,"given":"Christian","family":"Klemann","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery Hannover Medical School Hannover Germany"},{"name":"Department of Pediatric Pulmonology, Allergy and Neonatology Hannover Medical School Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,9,14]]},"reference":[{"issue":"2","key":"e_1_2_10_2_1","first-page":"82","article-title":",Biliary atresia: lessons learned from the voluntary German registry. 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