{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T10:58:17Z","timestamp":1790506697367,"version":"4.1.0"},"reference-count":48,"publisher":"Wiley","issue":"7-8","license":[{"start":{"date-parts":[[2018,6,19]],"date-time":"2018-06-19T00:00:00Z","timestamp":1529366400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100002338","name":"Ministry of Education of the People's Republic of China","doi-asserted-by":"publisher","award":["IRT_14R20"],"award-info":[{"award-number":["IRT_14R20"]}],"id":[{"id":"10.13039\/501100002338","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81571989"],"award-info":[{"award-number":["81571989"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81700529"],"award-info":[{"award-number":["81700529"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Gene Medicine"],"published-print":{"date-parts":[[2018,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Autoimmune hepatitis (AIH) is an inflammatory disease caused by an aberrant immune response to hepatic self\u2010antigens in which regulatory T cells (Tregs) are critical for maintaining immunosupression. The soluble form of fibrinogen\u2010like protein 2 (sFGL2), a novel effector molecule of Treg, is rarely investigated in AIH. In the present study, we dissected the role of sFGL2 in autoimmune hepatitis and its potential mechanism underlying AIH progression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Plasma and intrahepatic sFGL2 levels, as well as Treg cells, were measured in both AIH patients and experimental autoimmune hepatitis (EAH) mice. Th1, Th2, Th17 and Treg\u2010related cytokines were measured in the liver of EAH mice. Treg expression of sFgl2 and its effect on CD8+ T cell activity in EAH were assessed. The clinical relevance of sFGL2 in AIH\u2010associated inflammation and fibrosis was evaluated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Th17 responses is predominant in robust AIH patients and EAH mice. In AIH patients and EAH mice, the frequency of plasma Tregs was reduced, whereas intrahepatic Tregs were increased significantly. The plasma sFGL2 level was significantly higher at active phases compared to those during remission and was correlated with AIH progression. Enhanced sFGL2 expression was found in Tregs and inhibited conventional CD8+ T cells and Tc17 cell in EAH mice <jats:italic>ex vivo<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The Th17 response dominates autoimmune hepatitis progression. The increase in intrahepatic and plasma sFGL2 by Tregs may restrict AIH progression by inhibiting conventional CD8+ T cells and Tc17 cell function. The high correlation between sFGL2 and disease severity may predict AIH outcome.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jgm.3023","type":"journal-article","created":{"date-parts":[[2018,5,14]],"date-time":"2018-05-14T12:04:59Z","timestamp":1526299499000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Soluble Fgl2 restricts autoimmune hepatitis progression via suppressing Tc17 and conventional CD8+ T cell function"],"prefix":"10.1002","volume":"20","author":[{"given":"Guo","family":"Ai","sequence":"first","affiliation":[{"name":"Institute of Infectious Disease, Tongji Hospital of Tongji Medical College  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiming","family":"Yan","sequence":"additional","affiliation":[{"name":"Institute of Infectious Disease, Tongji Hospital of Tongji Medical College  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haijing","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease, Tongji Hospital of Tongji Medical College Huazhong University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Xiao","sequence":"additional","affiliation":[{"name":"Institute of Infectious Disease, Tongji Hospital of Tongji Medical College  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong","family":"Xi","sequence":"additional","affiliation":[{"name":"Institute of Infectious Disease, Tongji Hospital of Tongji Medical College  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease, Tongji Hospital of Tongji Medical College Huazhong University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaquan","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease, Tongji Hospital of Tongji Medical College Huazhong University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoping","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Tongji Hospital of Tongji Medical College Huazhong University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8871-2015","authenticated-orcid":false,"given":"Xiaoyang","family":"Wan","sequence":"additional","affiliation":[{"name":"Institute of Infectious Disease, Tongji Hospital of Tongji Medical College  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Ning","sequence":"additional","affiliation":[{"name":"Institute of Infectious Disease, Tongji Hospital of Tongji Medical College  Wuhan China"},{"name":"Department of Infectious Disease, Tongji Hospital of Tongji Medical College Huazhong University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,6,19]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2010.235259"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2014.05.034"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12072-010-9183-5"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.27991"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/512624"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.176.7.4484"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2012.02.029"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26583"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.27884"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.71.12.9223-9230.1997"},{"key":"e_1_2_6_12_1","doi-asserted-by":"crossref","first-page":"1789","DOI":"10.1016\/S0021-9258(18)52364-4","article-title":"Monoclonal antibody analysis of a unique macrophage procoagulant activity induced by murine hepatitis virus strain 3 infection","volume":"266","author":"Fung LS","year":"1991","journal-title":"J Biol Chem"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4615-5331-1_79"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI18114"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/molehr\/gah013"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0897.2003.01192.x"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22684"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.170.8.4036"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200838338"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840110106"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v13.i31.4249"},{"key":"e_1_2_6_22_1","unstructured":"CarberJC BarbeeRW BielitzkiJTet al.Guide for the Care and Use of Laboratory Animals 8th.National Research Council of the National Academes.2011."},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2007.07.006"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms17122007"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200939412"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.180.1.249"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0002639"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI65180"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1103111"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI63681"},{"key":"e_1_2_6_31_1","first-page":"325","article-title":"The duality of Fgl2\u2010secreted immune checkpoint regulator versus membrane\u2010associated procoagulant: therapeutic potential and implications","volume":"35","author":"Hu J","year":"2016","journal-title":"Int Rev Immunol"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00286.2002"},{"key":"e_1_2_6_33_1","first-page":"1780","article-title":"Serum level of transforming growth factor\u2010beta1 (TGF\u2010beta1) and the expression of TGF\u2010beta receptor type II in peripheral blood mononuclear cells in patients with autoimmune hepatitis","volume":"51","author":"Sakaguchi K","year":"2004","journal-title":"Hepatogastroenterology"},{"key":"e_1_2_6_34_1","doi-asserted-by":"crossref","first-page":"3299","DOI":"10.4049\/jimmunol.161.7.3299","article-title":"IL\u201010 is critical in the regulation of autoimmune encephalomyelitis as demonstrated by studies of IL\u201010\u2010 and IL\u20104\u2010deficient and transgenic mice","volume":"161","author":"Bettelli E","year":"1998","journal-title":"J Immunol"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.4172\/2155-9899.1000400"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(98)80230-4"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2009.05.002"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1005506031717"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-18818-5"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1872-034X.2011.00773.x"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2249.2001.01391.x"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/9829436"},{"key":"e_1_2_6_43_1","first-page":"150","article-title":"Serum IL\u201017 level predicts inflammatory activity in patients with autoimmune hepatitis","volume":"128","author":"Gutkowski K","year":"2018","journal-title":"Pol Arch Intern Med"},{"key":"e_1_2_6_44_1","first-page":"550","article-title":"Elevated circulating levels of IL\u201021 and IL\u201022 define a cytokine signature profile in type 2 autoimmune hepatitis patients","volume":"15","author":"Thomas\u2010Dupont P","year":"2016","journal-title":"Ann Hepatol"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.2337\/db10-0193"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2015.1058473"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2012.10.014"},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni1263"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2014.02.012"}],"container-title":["The Journal of Gene Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjgm.3023","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jgm.3023","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,17]],"date-time":"2023-09-17T19:20:11Z","timestamp":1694978411000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jgm.3023"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,6,19]]},"references-count":48,"journal-issue":{"issue":"7-8","published-print":{"date-parts":[[2018,7]]}},"alternative-id":["10.1002\/jgm.3023"],"URL":"https:\/\/doi.org\/10.1002\/jgm.3023","archive":["Portico"],"relation":{},"ISSN":["1099-498X","1521-2254"],"issn-type":[{"value":"1099-498X","type":"print"},{"value":"1521-2254","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,6,19]]},"assertion":[{"value":"2018-02-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-05-03","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-06-19","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e3023"}}