{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T16:33:15Z","timestamp":1787243595820,"version":"build-2736575974"},"reference-count":140,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,2,16]],"date-time":"2023-02-16T00:00:00Z","timestamp":1676505600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82202297, 81900573"],"award-info":[{"award-number":["82202297, 81900573"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017596","name":"Natural Science Basic Research Program of Shaanxi Province","doi-asserted-by":"publisher","award":["2022JQ-914"],"award-info":[{"award-number":["2022JQ-914"]}],"id":[{"id":"10.13039\/501100017596","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Hepatic fibrosis is often secondary to chronic inflammatory liver injury. During the development of hepatic fibrosis, the damaged hepatocytes and activated hepatic stellate cells (HSCs) caused by the pathogenic injury could secrete a variety of cytokines and chemokines, which will chemotactic innate and adaptive immune cells of liver tissue and peripheral circulation infiltrating into the injury site, mediating the immune response against injury and promoting tissue reparation. However, the continuous release of persistent injurious stimulus-induced inflammatory cytokines will promote HSCs-mediated fibrous tissue hyperproliferation and excessive repair, which will cause hepatic fibrosis development and progression to cirrhosis even liver cancer. And the activated HSCs can secrete various cytokines and chemokines, which directly interact with immune cells and actively participate in liver disease progression. Therefore, analyzing the changes in local immune homeostasis caused by immune response under different pathological states will greatly enrich our understanding of liver diseases\u2019 reversal, chronicity, progression, and even deterioration of liver cancer. In this review, we summarized the critical components of the hepatic immune microenvironment (HIME), different sub-type immune cells, and their released cytokines, according to their effect on the development of progression of hepatic fibrosis. And we also reviewed and analyzed the specific changes and the related mechanisms of the immune microenvironment in different chronic liver diseases.Moreover, we retrospectively analyzed whether the progression of hepatic fibrosis could be alleviated by modulating the HIME.We aimed to elucidate the pathogenesis of hepatic fibrosis and provide the possibility for exploring the therapeutic targets for hepatic fibrosis.<\/jats:p>","DOI":"10.3389\/fimmu.2023.1131588","type":"journal-article","created":{"date-parts":[[2023,2,16]],"date-time":"2023-02-16T05:17:56Z","timestamp":1676524676000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":23,"title":["Ongoing involvers and promising therapeutic targets of hepatic fibrosis: The hepatic immune microenvironment"],"prefix":"10.3389","volume":"14","author":[{"given":"Nana","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huimin","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhixuan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuoqun","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ran","family":"Ju","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayi","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heli","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoli","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Lv","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,2,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathol-011110-130246","article-title":"Pathogenesis of liver fibrosis","volume":"6","author":"Hernandez-Gea","year":"2011","journal-title":"Annu Rev Pathol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1177\/1535370219898141","article-title":"Mechanisms of liver fibrosis and its role in liver cancer","volume":"245","author":"Dhar","year":"2020","journal-title":"Exp Biol Med (Maywood N.J.)"},{"key":"B3","doi-asserted-by":"publisher","first-page":"14","DOI":"10.5152\/tjg.2018.17330","article-title":"Liver fibrosis","volume":"29","author":"Ayd\u0131n","year":"2018","journal-title":"Turkish J Gastroenterol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1007\/s12015-021-10286-9","article-title":"Stem cell-based therapy strategy for hepatic fibrosis by targeting intrahepatic cells","volume":"18","author":"Deng","year":"2021","journal-title":"Stem Cell Rev Rep"},{"key":"B5","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1038\/nrgastro.2017.38","article-title":"Mechanisms of hepatic stellate cell activation","volume":"14","author":"Tsuchida","year":"2017","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2020.104720","article-title":"Intercellular crosstalk of hepatic stellate cells in liver fibrosis: New insights into therapy","volume":"155","author":"Cai","year":"2020","journal-title":"Pharmacol Res"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1201840109","article-title":"Myofibroblasts revert to an inactive phenotype during regression of liver fibrosis","volume":"109","author":"Kisseleva","year":"2012","journal-title":"Proc Natl Acad Sci U.S.A."},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.27532","article-title":"Origin and role of hepatic myofibroblasts in hepatocellular carcinoma","volume":"11","author":"Yavuz","year":"2020","journal-title":"Oncotarget"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2019.117094","article-title":"Extracellular vesicles participate in macrophage-involved immune responses under liver diseases","volume":"240","author":"Jiajia","year":"2020","journal-title":"Life Sci"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-020-00592-6","article-title":"Gut microbiome, liver immunology, and liver diseases","volume":"18","author":"Wang","year":"2020","journal-title":"Cell Mol Immunol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-020-00372-7","article-title":"Molecular and cellular mechanisms of liver fibrosis and its regression","volume":"18","author":"Kisseleva","year":"2020","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1172\/JCI88881","article-title":"Liver inflammation and fibrosis","volume":"127","author":"Koyama","year":"2017","journal-title":"J Clin Invest"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.18053\/jctres.03.2017S1.003","article-title":"The impact of sterile inflammation in acute liver injury","volume":"3","author":"Woolbright","year":"2017","journal-title":"J Clin Trans Res"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.trre.2011.10.006","article-title":"Current strategies to minimize hepatic ischemia-reperfusion injury by targeting reactive oxygen species","volume":"26","author":"Jaeschke","year":"2012","journal-title":"Transplant Rev (Orlando)"},{"key":"B15","article-title":"Macrophages and alcohol-related liver inflammation","volume":"37","author":"Ju","year":"2015","journal-title":"Alcohol Res"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.3390\/cells10051097","article-title":"Pathophysiology and treatment options for hepatic fibrosis: Can it be completely cured","volume":"10","author":"Khanam","year":"2021","journal-title":"Cells"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2013.12.025","article-title":"Macrophage heterogeneity in liver injury and fibrosis","volume":"60","author":"Tacke","year":"2014","journal-title":"J Hepatol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2017.11","article-title":"Liver macrophages in tissue homeostasis and disease","volume":"17","author":"Krenkel","year":"2017","journal-title":"Nat Rev Immunol"},{"key":"B19","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1016\/bs.ircmb.2022.04.006","article-title":"Macrophages as key regulators of liver health and disease","volume":"368","author":"Papachristoforou","year":"2022","journal-title":"Int Rev Cell Mol Biol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmgh.2020.08.012","article-title":"Roles of CCR2 and CCR5 for hepatic macrophage polarization in mice with liver parenchymal cell-specific NEMO deletion","volume":"11","author":"Bartneck","year":"2021","journal-title":"Cell Mol Gastroenterol Hepatol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1111\/liv.14940","article-title":"Hepatic macrophages: Key players in the development and progression of liver fibrosis","volume":"41","author":"Cheng","year":"2021","journal-title":"Liver Int"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19051294","article-title":"TGF-beta and the tissue microenvironment: Relevance in fibrosis and cancer","volume":"19","author":"Caja","year":"2018","journal-title":"Int J Mol Sci"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2020.110586","article-title":"Polydatin attenuates hepatic stellate cell proliferation and liver fibrosis by suppressing sphingosine kinase 1","volume":"130","author":"Lan","year":"2020","journal-title":"BioMed Pharmacother"},{"key":"B24","doi-asserted-by":"publisher","first-page":"594","DOI":"10.1016\/j.jconrel.2021.03.016","article-title":"Matrix metalloproteinase-1 decorated polymersomes, a surface-active extracellular matrix therapeutic, potentiates collagen degradation and attenuates early liver fibrosis","volume":"332","author":"Geervliet","year":"2021","journal-title":"J Control Release"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2017.05.022","article-title":"Cytotherapy with M1-polarized macrophages ameliorates liver fibrosis by modulating immune microenvironment in mice","volume":"67","author":"Ma","year":"2017","journal-title":"J Hepatol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-020-00372-7","article-title":"Molecular and cellular mechanisms of liver fibrosis and its regression","volume":"18","author":"Kisseleva","year":"2021","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1038\/s41565-020-00832-w","article-title":"A relaxin-based nanotherapy for liver fibrosis","volume":"16","author":"Fallowfield","year":"2021","journal-title":"Nat Nanotechnol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1038\/s41565-020-00836-6","article-title":"Hepatic macrophages act as a central hub for relaxin-mediated alleviation of liver fibrosis","volume":"16","author":"Hu","year":"2021","journal-title":"Nat Nanotechnol"},{"key":"B29","doi-asserted-by":"publisher","first-page":"998","DOI":"10.1016\/j.bbadis.2013.01.005","article-title":"Dendritic cells and liver fibrosis","volume":"1832","author":"Rahman","year":"2013","journal-title":"Biochim Biophys Acta"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2022.106092","article-title":"Kinsenoside attenuates liver fibro-inflammation by suppressing dendritic cells via the PI3K-AKT-FoxO1 pathway","volume":"177","author":"Xiang","year":"2022","journal-title":"Pharmacol Res"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.971346","article-title":"Myeloid cells in alcoholic liver diseases: Mechanism and prospect","volume":"13","author":"Xu","year":"2022","journal-title":"Front Immunol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00563","article-title":"Targeting myeloid-derived cells: New frontiers in the treatment of non-alcoholic and alcoholic liver disease","volume":"10","author":"Vonghia","year":"2019","journal-title":"Front Immunol"},{"key":"B33","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1038\/cmi.2011.53","article-title":"Liver fibrosis: mechanisms of immune-mediated liver injury","volume":"9","author":"Xu","year":"2012","journal-title":"Cell Mol Immunol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1002\/hep.24621","article-title":"Dendritic cell regulation of carbon tetrachloride-induced murine liver fibrosis regression","volume":"55","author":"Jiao","year":"2012","journal-title":"Hepatology"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.6A0114-004RR","article-title":"Chronic alcohol ingestion modulates hepatic macrophage populations and functions in mice","volume":"96","author":"Wang","year":"2014","journal-title":"J Leukoc Biol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2020.107166","article-title":"Sex specific effect of alcohol on hepatic plasmacytoid dendritic cells","volume":"90","author":"Alharshawi","year":"2021","journal-title":"Int Immunopharmacol"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00477","article-title":"gammadeltaT cells suppress liver fibrosis via strong cytolysis and enhanced NK cell-mediated cytotoxicity against hepatic stellate cells","volume":"10","author":"Liu","year":"2019","journal-title":"Front Immunol"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2022.12724","article-title":"Crosstalk between NK cells and hepatic stellate cells in liver fibrosis (Review)","volume":"25","author":"Zhang","year":"2022","journal-title":"Mol Med Rep"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01582","article-title":"The roles of liver-resident lymphocytes in liver diseases","volume":"10","author":"Wang","year":"2019","journal-title":"Front Immunol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm.2014.1831","article-title":"Hydrodynamics-based transfection of rat interleukin-10 gene attenuates porcine serum-induced liver fibrosis in rats by inhibiting the activation of hepatic stellate cells","volume":"34","author":"Huang","year":"2014","journal-title":"Int J Mol Med"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1111\/acer.12167","article-title":"TGF-beta1 up-regulates the expression of PDGF-beta receptor mRNA and induces a delayed PI3K-, AKT-, and p70(S6K) -dependent proliferative response in activated hepatic stellate cells","volume":"37","author":"Shah","year":"2013","journal-title":"Alcohol Clin Exp Res"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.2012.54","article-title":"NK cells from HCV-infected patients effectively induce apoptosis of activated primary human hepatic stellate cells in a TRAIL-, FasL- and NKG2D-dependent manner","volume":"92","author":"Glassner","year":"2012","journal-title":"Lab Invest"},{"key":"B43","doi-asserted-by":"publisher","first-page":"598","DOI":"10.1111\/liv.14307","article-title":"Hepatic NK cells attenuate fibrosis progression of non-alcoholic steatohepatitis in dependent of CXCL10-mediated recruitment","volume":"40","author":"Fan","year":"2020","journal-title":"Liver Int"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2019.109445","article-title":"Interleukin-10 induces senescence of activated hepatic stellate cells via STAT3-p53 pathway to attenuate liver fibrosis","volume":"66","author":"Huang","year":"2020","journal-title":"Cell Signal"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1002\/hep.31875","article-title":"Metabotropic glutamate receptor 5 in natural killer cells attenuates liver fibrosis by exerting cytotoxicity to activated stellate cells","volume":"74","author":"Choi","year":"2021","journal-title":"Hepatology"},{"key":"B46","doi-asserted-by":"publisher","first-page":"799","DOI":"10.1002\/hep.28389","article-title":"NKp46(+) natural killer cells attenuate metabolism-induced hepatic fibrosis by regulating macrophage activation in mice","volume":"63","author":"Tosello-Trampont","year":"2016","journal-title":"Hepatology"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2019.03.012","article-title":"KLRG1+ natural killer cells exert a novel antifibrotic function in chronic hepatitis b","volume":"71","author":"Wijaya","year":"2019","journal-title":"J Hepatol"},{"key":"B48","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.yexcr.2016.01.012","article-title":"Vitamin a and insulin are required for the maintenance of hepatic stellate cell quiescence","volume":"341","author":"Yoneda","year":"2016","journal-title":"Exp Cell Res"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1080\/07853890.2022.2108894","article-title":"A comparative study on roles of natural killer T cells in two diet-induced non-alcoholic steatohepatitis-related fibrosis in mice","volume":"54","author":"Zheng","year":"2022","journal-title":"Ann Med"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1038\/nri3623","article-title":"Liver fibrosis and repair: immune regulation of wound healing in a solid organ","volume":"14","author":"Pellicoro","year":"2014","journal-title":"Nat Rev Immunol"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1016\/s1499-3872(17)60014-6","article-title":"Crosstalk of liver immune cells and cell death mechanisms in different murine models of liver injury and its clinical relevance","volume":"16","author":"Khan","year":"2017","journal-title":"Hepatobiliary Pancreat Dis Int"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1586\/17474124.2015.1056738","article-title":"Natural killer T cells in liver injury, inflammation and cancer","volume":"9","author":"Wang","year":"2015","journal-title":"Expert Rev Gastroenterol Hepatol"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02082","article-title":"Complex network of NKT cell subsets controls immune homeostasis in liver and gut","volume":"9","author":"Marrero","year":"2018","journal-title":"Front Immunol"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.5858\/2009-0144-OA.1","article-title":"Production and activation of matrix metalloproteinase 7 (matrilysin 1) in the lungs of patients with idiopathic pulmonary fibrosis","volume":"134","author":"Fujishima","year":"2010","journal-title":"Arch Pathol Lab Med"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1007\/s00436-016-5012-7","article-title":"Interleukin-13 is involved in the formation of liver fibrosis in clonorchis sinensis-infected mice","volume":"115","author":"Xu","year":"2016","journal-title":"Parasitol Res"},{"key":"B56","doi-asserted-by":"publisher","first-page":"3260","DOI":"10.1038\/s41598-019-40078-8","article-title":"Inflammatory cytokines and change of Th1\/Th2 balance as prognostic indicators for hepatocellular carcinoma in patients treated with transarterial chemoembolization","volume":"9","author":"Lee","year":"2019","journal-title":"Sci Rep"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00193.2013","article-title":"IFN-gamma deficiency attenuates hepatic inflammation and fibrosis in a steatohepatitis model induced by a methionine- and choline-deficient high-fat diet","volume":"305","author":"Luo","year":"2013","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2014.09.003","article-title":"Metabolic activation of intrahepatic CD8+ T cells and NKT cells causes nonalcoholic steatohepatitis and liver cancer via cross-talk with hepatocytes","volume":"26","author":"Wolf","year":"2014","journal-title":"Cancer Cell"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03233-8","article-title":"Auto-aggressive CXCR6(+) CD8 T cells cause liver immune pathology in NASH","volume":"592","author":"Dudek","year":"2021","journal-title":"Nature"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-021-00639-3","article-title":"Immune cell-mediated features of non-alcoholic steatohepatitis","volume":"22","author":"Huby","year":"2022","journal-title":"Nat Rev Immunol"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1002\/hep.29636","article-title":"B lymphocytes limit senescence-driven fibrosis resolution and favor hepatocarcinogenesis in mouse liver injury","volume":"67","author":"Faggioli","year":"2018","journal-title":"Hepatology"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1038\/icb.2016.116","article-title":"The pro-fibrotic role of dipeptidyl peptidase 4 in carbon tetrachloride-induced experimental liver injury","volume":"95","author":"Wang","year":"2017","journal-title":"Immunol Cell Biol"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.661196","article-title":"The role of b cells and b cell therapies in immune-mediated liver diseases","volume":"12","author":"Cargill","year":"2021","journal-title":"Front Immunol"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1402256","article-title":"Cutting edge: CD69 interference with sphingosine-1-phosphate receptor function regulates peripheral T cell retention","volume":"194","author":"Mackay","year":"2015","journal-title":"J Immunol"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12087","article-title":"Tissue-resident memory T cells","volume":"255","author":"Shin","year":"2013","journal-title":"Immunol Rev"},{"key":"B66","doi-asserted-by":"publisher","first-page":"4474","DOI":"10.1038\/s41467-021-24734-0","article-title":"CD8(+) tissue-resident memory T cells promote liver fibrosis resolution by inducing apoptosis of hepatic stellate cells","volume":"12","author":"Koda","year":"2021","journal-title":"Nat Commun"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-022-00932-w","article-title":"Liver-resident memory T cells: life in lockdown","volume":"44","author":"Pallett","year":"2022","journal-title":"Semin Immunopathol"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1007\/s11684-017-0584-x","article-title":"Gammadelta T cells in liver diseases","volume":"12","author":"Wang","year":"2018","journal-title":"Front Med"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.891687","article-title":"Comparing mouse and human tissue-resident gammadelta T cells","volume":"13","author":"Qu","year":"2022","journal-title":"Front Immunol"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22034","article-title":"Liver: An organ with predominant innate immunity","volume":"47","author":"Gao","year":"2008","journal-title":"Hepatology"},{"key":"B71","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1038\/s41419-022-04739-3","article-title":"IL-1beta-activated mTORC2 promotes accumulation of IFN-gamma(+) gammadelta T cells by upregulating CXCR3 to restrict hepatic fibrosis","volume":"13","author":"Liu","year":"2022","journal-title":"Cell Death Dis"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26697","article-title":"Chemokine receptor CCR6-dependent accumulation of gammadelta T cells in injured liver restricts hepatic inflammation and fibrosis","volume":"59","author":"Hammerich","year":"2014","journal-title":"Hepatology"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1002\/hep.28644","article-title":"Exosome-mediated activation of toll-like receptor 3 in stellate cells stimulates interleukin-17 production by gammadelta T cells in liver fibrosis","volume":"64","author":"Seo","year":"2016","journal-title":"Hepatology"},{"key":"B74","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/j.jaut.2013.08.004","article-title":"Autoimmune hepatitis: Contrasts and comparisons in children and adults - a comprehensive review","volume":"46","author":"Floreani","year":"2013","journal-title":"J Autoimmun"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2015.04.005","article-title":"Regulatory b cells: origin, phenotype, and function","volume":"42","author":"Rosser","year":"2015","journal-title":"Immunity"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1042\/CS20160069","article-title":"IL-10-producing regulatory b-cells suppressed effector T-cells but enhanced regulatory T-cells in chronic HBV infection","volume":"130","author":"Liu","year":"2016","journal-title":"Clin Sci (Lond)"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01169","article-title":"Crosstalk between liver macrophages and surrounding cells in nonalcoholic steatohepatitis","volume":"11","author":"Li","year":"2020","journal-title":"Front Immunol"},{"key":"B78","unstructured":"Global hepatitis report2017"},{"key":"B79","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1016\/S0140-6736(22)01377-0","article-title":"Viral hepatitis elimination: A challenge, but within reach","volume":"400","author":"The","year":"2022","journal-title":"Lancet"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1111\/liv.12255","article-title":"Hepatic stellate cells that coexpress LRAT and CRBP-1 partially contribute to portal fibrogenesis in patients with human viral hepatitis","volume":"34","author":"Nagatsuma","year":"2014","journal-title":"Liver Int"},{"key":"B81","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1186\/s12916-021-02085-3","article-title":"HBeAg mediates inflammatory functions of macrophages by TLR2 contributing to hepatic fibrosis","volume":"19","author":"Xie","year":"2021","journal-title":"BMC Med"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.543769","article-title":"Transcriptional repression of the transforming growth factor beta (TGF-beta) pseudoreceptor BMP and activin membrane-bound inhibitor (BAMBI) by nuclear factor kappaB (NF-kappaB) p50 enhances TGF-beta signaling in hepatic stellate cells","volume":"289","author":"Liu","year":"2014","journal-title":"J Biol Chem"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1007\/s00204-018-2278-9","article-title":"MicroRNA-942 mediates hepatic stellate cell activation by regulating BAMBI expression in human liver fibrosis","volume":"92","author":"Tao","year":"2018","journal-title":"Arch Toxicol"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2013.01.036","article-title":"Antifibrotic effects of a recombinant adeno-associated virus carrying small interfering RNA targeting TIMP-1 in rat liver fibrosis","volume":"182","author":"Cong","year":"2013","journal-title":"Am J Pathol"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2010.03.052","article-title":"Toll-like receptor 9 promotes steatohepatitis by induction of interleukin-1beta in mice","volume":"139","author":"Miura","year":"2010","journal-title":"Gastroenterology"},{"key":"B86","doi-asserted-by":"publisher","first-page":"1","DOI":"10.14218\/JCTH.2022.00005","article-title":"Upregulation of GLT25D1 in hepatic stellate cells promotes liver fibrosis via the TGF-beta1\/SMAD3 pathway In vivo and In vitro","volume":"11","author":"Wang","year":"2023","journal-title":"J Clin Transl Hepatol"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.3390\/cells9010188","article-title":"Are liver pericytes just precursors of myofibroblasts in hepatic diseases? insights from the crosstalk between perivascular and inflammatory cells in liver injury and repair","volume":"9","author":"Da","year":"2020","journal-title":"Cells"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2013.04.098","article-title":"Hepatitis b virus e antigen induces activation of rat hepatic stellate cells","volume":"435","author":"Zan","year":"2013","journal-title":"Biochem Biophys Res Commun"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.3390\/ijms231810777","article-title":"Hepatic stellate cell modulates the immune microenvironment in the progression of hepatocellular carcinoma","volume":"23","author":"Wang","year":"2022","journal-title":"Int J Mol Sci"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002594","article-title":"TGF-beta1 down-regulation of NKG2D\/DAP10 and 2B4\/SAP expression on human NK cells contributes to HBV persistence","volume":"8","author":"Sun","year":"2012","journal-title":"PloS Pathog"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2010.07.009","article-title":"Viral load reduction improves activation and function of natural killer cells in patients with chronic hepatitis b","volume":"54","author":"Tjwa","year":"2011","journal-title":"J Hepatol"},{"key":"B92","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/j.cytogfr.2015.10.002","article-title":"The PDGF system and its antagonists in liver fibrosis","volume":"28","author":"Borkham-Kamphorst","year":"2016","journal-title":"Cytokine Growth Factor Rev"},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2015.01.036","article-title":"Beta-PDGF receptor expressed by hepatic stellate cells regulates fibrosis in murine liver injury, but not carcinogenesis","volume":"63","author":"Kocabayoglu","year":"2015","journal-title":"J Hepatol"},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm.2012.1148","article-title":"HBV promotes the proliferation of hepatic stellate cells via the PDGF-B\/PDGFR-beta signaling pathway in vitro","volume":"30","author":"Bai","year":"2012","journal-title":"Int J Mol Med"},{"key":"B95","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02225-16","article-title":"Exosome-mediated intercellular communication between hepatitis c virus-infected hepatocytes and hepatic stellate cells","volume":"91","author":"Devhare","year":"2017","journal-title":"J Virol"},{"key":"B96","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtn.2019.01.006","article-title":"Exosomal transmission of MicroRNA from HCV replicating cells stimulates transdifferentiation in hepatic stellate cells","volume":"14","author":"Kim","year":"2019","journal-title":"Mol Ther Nucleic Acids"},{"key":"B97","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1056\/NEJMra050408","article-title":"Autoimmune hepatitis","volume":"354","author":"Krawitt","year":"2006","journal-title":"N Engl J Med"},{"key":"B98","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201847965","article-title":"CCL21-expression and accumulation of CCR7(+) NK cells in livers of patients with primary sclerosing cholangitis","volume":"49","author":"Langeneckert","year":"2019","journal-title":"Eur J Immunol"},{"key":"B99","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2022.113512","article-title":"Aberrant peribiliary gland niche exacerbates fibrosis in primary sclerosing cholangitis and a potential therapeutic strategy","volume":"153","author":"Wu","year":"2022","journal-title":"BioMed Pharmacother"},{"key":"B100","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26583","article-title":"Dysfunctional CD39(POS) regulatory T cells and aberrant control of T-helper type 17 cells in autoimmune hepatitis","volume":"59","author":"Grant","year":"2014","journal-title":"Hepatology"},{"key":"B101","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2013.12.027","article-title":"Reduced FOXP3(+) regulatory T cells in patients with primary sclerosing cholangitis are associated with IL2RA gene polymorphisms","volume":"60","author":"Sebode","year":"2014","journal-title":"J Hepatol"},{"key":"B102","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-021-00790-w","article-title":"Activation of AMPKalpha1 is essential for regulatory T cell function and autoimmune liver disease prevention","volume":"18","author":"Zhu","year":"2021","journal-title":"Cell Mol Immunol"},{"key":"B103","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0901216","article-title":"Distinct roles for CCR4 and CXCR3 in the recruitment and positioning of regulatory T cells in the inflamed human liver","volume":"184","author":"Oo","year":"2010","journal-title":"J Immunol"},{"key":"B104","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26447","article-title":"Increased T helper type 17 response to pathogen stimulation in patients with primary sclerosing cholangitis","volume":"58","author":"Katt","year":"2013","journal-title":"Hepatology"},{"key":"B105","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v23.i21.3832","article-title":"Clinical significance of changes in the Th17\/Treg ratio in autoimmune liver disease","volume":"23","author":"Feng","year":"2017","journal-title":"World J Gastroenterol"},{"key":"B106","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1016\/j.stem.2021.02.011","article-title":"Mitochondria as signaling organelles control mammalian stem cell fate","volume":"28","author":"Chakrabarty","year":"2021","journal-title":"Cell Stem Cell"},{"key":"B107","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-020-00354-w","article-title":"NAD(+) metabolism, stemness, the immune response, and cancer","volume":"6","author":"Navas","year":"2021","journal-title":"Signal Transduct Target Ther"},{"key":"B108","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2012.09.008","article-title":"Sterile inflammation in the liver","volume":"143","author":"Kubes","year":"2012","journal-title":"Gastroenterology"},{"key":"B109","doi-asserted-by":"publisher","DOI":"10.1002\/hep.29051","article-title":"An endoplasmic reticulum protein, nogo-b, facilitates alcoholic liver disease through regulation of kupffer cell polarization","volume":"65","author":"Park","year":"2017","journal-title":"Hepatol (Baltimore Md.)"},{"key":"B110","doi-asserted-by":"publisher","DOI":"10.1055\/s-0040-1708876","article-title":"Hepatic stellate cell-macrophage crosstalk in liver fibrosis and carcinogenesis","volume":"40","author":"Matsuda","year":"2020","journal-title":"Semin Liver Dis"},{"key":"B111","doi-asserted-by":"publisher","DOI":"10.1038\/srep18685","article-title":"Telomerase reverse transcriptase acts in a feedback loop with NF-\u03baB pathway to regulate macrophage polarization in alcoholic liver disease","volume":"6","author":"Wu","year":"2016","journal-title":"Sci Rep"},{"key":"B112","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26592","article-title":"NLRP3 inflammasome activation results in hepatocyte pyroptosis, liver inflammation, and fibrosis in mice","volume":"59","author":"Wree","year":"2014","journal-title":"Hepatol (Baltimore Md.)"},{"key":"B113","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2020.08.006","article-title":"Cyanidin-3-O-\u03b2-glucoside inactivates NLRP3 inflammasome and alleviates alcoholic steatohepatitis via SirT1\/NF-\u03baB signaling pathway","volume":"160","author":"Yujia","year":"2020","journal-title":"Free Radic Biol Med"},{"key":"B114","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2019.01459","article-title":"Magnolol prevents acute alcoholic liver damage by activating PI3K\/Nrf2\/PPARgamma and inhibiting NLRP3 signaling pathway","volume":"10","author":"Liu","year":"2019","journal-title":"Front Pharmacol"},{"key":"B115","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2016.12.017","article-title":"Purinergic P2X7 receptor mediates acetaldehyde-induced hepatic stellate cells activation via PKC-dependent GSK3beta pathway","volume":"43","author":"Wu","year":"2017","journal-title":"Int Immunopharmacol"},{"key":"B116","doi-asserted-by":"publisher","DOI":"10.1038\/srep18685","article-title":"Telomerase reverse transcriptase acts in a feedback loop with NF-kappaB pathway to regulate macrophage polarization in alcoholic liver disease","volume":"6","author":"Wu","year":"2016","journal-title":"Sci Rep"},{"key":"B117","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2014.07.018","article-title":"Cell death and cell death responses in liver disease: Mechanisms and clinical relevance","volume":"147","author":"Tom","year":"2014","journal-title":"Gastroenterology"},{"key":"B118","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2017.05.021","article-title":"CD39 limits P2X7 receptor inflammatory signaling and attenuates sepsis-induced liver injury","volume":"67","author":"Luiz","year":"2017","journal-title":"J Hepatol"},{"key":"B119","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2008.156307","article-title":"Toll-like receptors as targets in chronic liver diseases","volume":"58","author":"Mencin","year":"2009","journal-title":"Gut"},{"key":"B120","doi-asserted-by":"publisher","DOI":"10.1038\/nm1663","article-title":"TLR4 enhances TGF-beta signaling and hepatic fibrosis","volume":"13","author":"Seki","year":"2007","journal-title":"Nat Med"},{"key":"B121","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2016.01.035","article-title":"The pro-inflammatory effects of miR-155 promote liver fibrosis and alcohol-induced steatohepatitis","volume":"64","author":"Shashi","year":"2016","journal-title":"J Hepatol"},{"key":"B122","doi-asserted-by":"publisher","DOI":"10.7861\/clinmedicine.18-3-245","article-title":"Non-alcoholic fatty liver disease","volume":"18","author":"Maurice","year":"2018","journal-title":"Clin Med (London England)"},{"key":"B123","doi-asserted-by":"publisher","DOI":"10.1002\/hep.31755","article-title":"Microbiota-driven activation of intrahepatic b cells aggravates nonalcoholic steatohepatitis through innate and adaptive signaling","volume":"74","author":"Barrow","year":"2021","journal-title":"Hepatol (Baltimore Md.)"},{"key":"B124","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2017.05.018","article-title":"IL-6\/Stat3-Dependent induction of a distinct, obesity-associated NK cell subpopulation deteriorates energy and glucose homeostasis","volume":"26","author":"Sebastian","year":"2017","journal-title":"Cell Metab"},{"key":"B125","doi-asserted-by":"publisher","DOI":"10.1042\/CS20150405","article-title":"The balance between IL-17 and IL-22 produced by liver-infiltrating T-helper cells critically controls NASH development in mice","volume":"130","author":"Rolla","year":"2016","journal-title":"Clin Sci (London Engl 1979)"},{"key":"B126","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.aai7616","article-title":"Type I interferon responses drive intrahepatic T cells to promote metabolic syndrome","volume":"2","author":"Magar","year":"2017","journal-title":"Sci Immunol"},{"key":"B127","doi-asserted-by":"publisher","first-page":"2247","DOI":"10.1038\/s41467-017-02325-2","article-title":"Pro-inflammatory hepatic macrophages generate ROS through NADPH oxidase 2 via endocytosis of monomeric TLR4-MD2 complex","volume":"8","author":"Kim","year":"2017","journal-title":"Nat Commun"},{"key":"B128","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2015.08.001","article-title":"Implications of microbiota and bile acid in liver injury and regeneration","volume":"63","author":"Liu","year":"2015","journal-title":"J Hepatol"},{"key":"B129","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abe1692","article-title":"Hepatocyte TLR4 triggers inter-hepatocyte Jagged1\/Notch signaling to determine NASH-induced fibrosis","volume":"13","author":"Yu","year":"2021","journal-title":"Sci Transl Med"},{"key":"B130","doi-asserted-by":"publisher","DOI":"10.1002\/iub.1348","article-title":"Tetramethylpyrazine reduces inflammation in liver fibrosis and inhibits inflammatory cytokine expression in hepatic stellate cells by modulating NLRP3 inflammasome pathway","volume":"67","author":"Wu","year":"2015","journal-title":"IUBMB Life"},{"key":"B131","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v24.i42.4759","article-title":"Yiguanjian decoction enhances fetal liver stem\/progenitor cell-mediated repair of liver cirrhosis through regulation of macrophage activation state","volume":"24","author":"Xu","year":"2018","journal-title":"World J Gastroenterol"},{"key":"B132","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2017.11.047","article-title":"Lycium barbarum polysaccharides improve CCl(4)-induced liver fibrosis, inflammatory response and TLRs\/NF-kB signaling pathway expression in wistar rats","volume":"192","author":"Gan","year":"2018","journal-title":"Life Sci"},{"key":"B133","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/4652596","article-title":"Interleukin 10 gene-modified bone marrow-derived dendritic cells attenuate liver fibrosis in mice by inducing regulatory T cells and inhibiting the TGF-beta\/Smad signaling pathway","volume":"2019","author":"Xu","year":"2019","journal-title":"Mediators Inflammation"},{"key":"B134","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2022.113834","article-title":"Si-Wu-Tang ameliorates bile duct ligation-induced liver fibrosis via modulating immune environment","volume":"155","author":"Ma","year":"2022","journal-title":"BioMed Pharmacother"},{"key":"B135","doi-asserted-by":"publisher","DOI":"10.1039\/D1FO03768D","article-title":"Chitooligosaccharides alleviate hepatic fibrosis by regulating the polarization of M1 and M2 macrophages","volume":"13","author":"Liu","year":"2021","journal-title":"Food Funct"},{"key":"B136","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2018.07.028","article-title":"Curcumin reduces Ly6C(hi) monocyte infiltration to protect against liver fibrosis by inhibiting kupffer cells activation to reduce chemokines secretion","volume":"106","author":"Zhao","year":"2018","journal-title":"BioMed Pharmacother"},{"key":"B137","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20212414","article-title":"EP3 enhances adhesion and cytotoxicity of NK cells toward hepatic stellate cells in a murine liver fibrosis model","volume":"219","author":"Tao","year":"2022","journal-title":"J Exp Med"},{"key":"B138","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2021-325150","article-title":"FSTL1 promotes liver fibrosis by reprogramming macrophage function through modulating the intracellular function of PKM2","volume":"71","author":"Rao","year":"2022","journal-title":"Gut"},{"key":"B139","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1016\/j.jhep.2021.09.032","article-title":"Dopamine receptor D2 antagonism normalizes profibrotic macrophage-endothelial crosstalk in non-alcoholic steatohepatitis","volume":"76","author":"Qing","year":"2022","journal-title":"J Hepatol"},{"key":"B140","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23126696","article-title":"Combined therapy with a CCR2\/CCR5 antagonist and FGF21 analogue synergizes in ameliorating steatohepatitis and fibrosis","volume":"23","author":"Puengel","year":"2022","journal-title":"Int J Mol Sci"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2023.1131588\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,16]],"date-time":"2023-02-16T05:18:00Z","timestamp":1676524680000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2023.1131588\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,16]]},"references-count":140,"alternative-id":["10.3389\/fimmu.2023.1131588"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2023.1131588","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,16]]},"article-number":"1131588"}}