{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T21:08:48Z","timestamp":1790888928295,"version":"4.1.0"},"reference-count":34,"publisher":"Portland Press Ltd.","issue":"24","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2018,12,21]]},"abstract":"<jats:p>Type 3 innate lymphoid cell (ILC3) has recently emerged as a crucial effector in inflammatory and fibrotic diseases. The present study was designed to determine the roles of ILC3 in liver fibrosis. By flow cytometry, we documented increased frequencies of peripheral ILC3 (Lin\u2212CD127+CD117+CD294\u2212 lymphocytes) in patients, especially at the advanced stage of hepatitis B virus (HBV)-related chronic liver diseases, and demonstrated their correlations with disease progression. The in vitro fibrogenic effects by ILC3 were determined by co-culture experiments with LX-2 (a human hepatic stellate cell (HSC) line). The data indicate that pathogenic ILC3 can directly promote LX-2 fibrogenesis in non-contact manners by producing interleukin (IL)-17A and IL-22. Additionally, they had indirect fibrogenic effects by producing IL-22 to suppress interferon (IFN)-\u03b3 (a well-known anti-fibrotic cytokine) production by other immune cells. In carbon tetrachloride (CCl4)-induced wild-type mouse liver fibrosis models, we also documented significantly increased frequencies of both non-natural killer (NK) ILC (Lin\u2212CD127+ lymphocytes) and ILC3 (Lin\u2212CD127+ROR\u03b3t+ lymphocytes) in liver and spleen specimens. Furthermore, the ILC3 from fibrotic mice contained more IL-17A+ILC3 and IL-22+ILC3 subsets than those from normal and less-fibrotic mice. The in vivo effects of ILC3 in liver fibrogenesis were further determined using RAG-1\u2212\/\u2212 mice with ILC depletion and further adoptive transfer of ILC3 from wild-type mice. The immunohistochemical staining of liver specimens showed the beneficial effects by ILC depletion and the detrimental effects by ILC3 transfer in CCl4-induced mouse liver fibrosis models. Collectively, ILC3 plays a pro-fibrotic role in liver fibrosis progression.<\/jats:p>","DOI":"10.1042\/cs20180482","type":"journal-article","created":{"date-parts":[[2018,11,20]],"date-time":"2018-11-20T12:15:10Z","timestamp":1542716110000},"page":"2565-2582","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":61,"title":["Type 3 innate lymphoid cell: a new player in liver fibrosis progression"],"prefix":"10.1042","volume":"132","author":[{"given":"Siqi","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Tongji Hospital, Tongji University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengdi","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisha","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weimin","family":"She","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changqing","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Tongji Hospital, Tongji University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiyao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9354-6699","authenticated-orcid":false,"given":"Wei","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2018,12,13]]},"reference":[{"key":"2021113010595267800_B1","doi-asserted-by":"publisher","first-page":"1399","DOI":"10.1016\/S1473-3099(16)30204-3","article-title":"Requirements for global elimination of hepatitis B: a modelling study","volume":"16","author":"Nayagam","year":"2016","journal-title":"Lancet Infect. 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