{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T06:57:18Z","timestamp":1793429838888,"version":"4.5.0"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,12,22]],"date-time":"2022-12-22T00:00:00Z","timestamp":1671667200000},"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":["81771722,  81901630"],"award-info":[{"award-number":["81771722,  81901630"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Liver fibrosis is a poor outcome of patients with schistosomiasis, impacting the quality of life and even survival. Eggs deposited in the liver were the main pathogenic factors of hepatic fibrosis in Schistosomiasis japonica. However, the mechanism of hepatic fibrosis in schistosomiasis remains not well defined and there is no effective measure to prevent and treat schistosome-induced hepatic fibrosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this study, we applied single-cell sequencing to primarily explore the mechanism of hepatic fibrosis in murine schistosomiasis japonica (n=1) and normal mouse was served as control (n=1).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 10,403 cells were included in our analysis and grouped into 18 major cell clusters. Th2 cells and NKT cells were obviously increased and there was a close communication between NKT cells and FASLG signaling pathway. Flow cytometry analysis indicated that the expression of Fasl in NKT cells, CD8+ T cell and NK cell were higher in SJ groups. <jats:italic>Arg1<\/jats:italic>, <jats:italic>Retnla<\/jats:italic> and <jats:italic>Chil3<\/jats:italic>, marker genes of alternatively activated macrophages (M2), were mainly expressed in mononuclear phagocyte(1) (MP(1)), suggesting that Kupffer cells might undergo M2-like polarization in fibrotic liver of schistosomiasis. CXCL and CCL signaling pathway analysis with CellChat showed that Cxcl16-Cxcr6, Ccl6-Ccr2 and Ccl5-Ccr5 were the most dominant L\u2212R and there were close interactions between T cells and MPs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our research profiled a preliminary immunological network of hepatic fibrosis in murine schistosomiasis japonica, which might contribute to a better understanding of the mechanisms of liver fibrosis in schistosomiasis. NKT cells and CXCL and CCL signaling pathway such as Cxcl16-Cxcr6, Ccl6-Ccr2 and Ccl5-Ccr5 might be potential targets to alleviate hepatic fibrosis of schistosomiasis.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2022.980872","type":"journal-article","created":{"date-parts":[[2022,12,22]],"date-time":"2022-12-22T11:03:14Z","timestamp":1671706994000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":14,"title":["Single-cell RNA sequencing to dissect the immunological network of liver fibrosis in Schistosoma japonicum-infected mice"],"prefix":"10.3389","volume":"13","author":[{"given":"Yu","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junhui","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaoqin","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingzi","family":"Ming","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,12,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(22)00221-3","article-title":"Review of 2022 WHO guidelines on the control and elimination of schistosomiasis","volume":"22","author":"Lo","year":"2022","journal-title":"Lancet Infect Dis"},{"key":"B2","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1038\/s41572-018-0013-8","article-title":"Schistosomiasis","volume":"4","author":"McManus","year":"2018","journal-title":"Nat Rev Dis Primers"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2019.08.028","article-title":"Derivation and external validation of a model to predict 2-year mortality risk of patients with advanced schistosomiasis after discharge","volume":"47","author":"Li","year":"2019","journal-title":"EBioMedicine"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.pt.2018.02.005","article-title":"Schistosome-induced fibrotic disease: The role of hepatic stellate cells","volume":"34","author":"Carson","year":"2018","journal-title":"Trends Parasitol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/j.addr.2017.05.007","article-title":"Hepatic stellate cells as key target in liver fibrosis","volume":"121","author":"Higashi","year":"2017","journal-title":"Advanced Drug delivery Rev"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.00061","article-title":"T Lymphocyte-mediated liver immunopathology of schistosomiasis","volume":"11","author":"Zheng","year":"2020","journal-title":"Front Immunol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3390\/cells8101262","article-title":"Inhibition of rho-kinase downregulates Th17 cells and ameliorates hepatic fibrosis by schistosoma japonicum infection","volume":"8","author":"Zhou","year":"2019","journal-title":"Cells"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.14950","article-title":"Follicular helper T cells recruit eosinophils into host liver by producing CXCL12 during schistosoma japonicum infection","volume":"24","author":"Chen","year":"2020","journal-title":"J Cell Mol Med"},{"key":"B9","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1111\/imm.13111","article-title":"Interleukin-9 blockage reduces early hepatic granuloma formation and fibrosis during schistosoma japonicum infection in mice","volume":"158","author":"Zhan","year":"2019","journal-title":"Immunology"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.176.10.5839","article-title":"Regulatory T cell responses develop in parallel to Th responses and control the magnitude and phenotype of the Th effector population","volume":"176","author":"Taylor","year":"2006","journal-title":"J Immunol (Baltimore Md. 1950)"},{"key":"B11","doi-asserted-by":"publisher","first-page":"16035","DOI":"10.1038\/ncomms16035","article-title":"Innate scavenger receptor-a regulates adaptive T helper cell responses to pathogen infection","volume":"8","author":"Xu","year":"2017","journal-title":"Nat Commun"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.pt.2013.12.009","article-title":"Cellular and chemokine-mediated regulation in schistosome-induced hepatic pathology","volume":"30","author":"Chuah","year":"2014","journal-title":"Trends Parasitol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(04)00107-4","article-title":"Alternative macrophage activation is essential for survival during schistosomiasis and downmodulates T helper 1 responses and immunopathology","volume":"20","author":"Herbert","year":"2004","journal-title":"Immunity"},{"key":"B14","doi-asserted-by":"publisher","first-page":"e1000371","DOI":"10.1371\/journal.ppat.1000371","article-title":"Arginase-1-expressing macrophages suppress Th2 cytokine-driven inflammation and fibrosis","volume":"5","author":"Pesce","year":"2009","journal-title":"PloS Pathog"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.pt.2012.09.005","article-title":"Role of resident liver cells in the pathogenesis of schistosomiasis","volume":"28","author":"Anthony","year":"2012","journal-title":"Trends Parasitol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(06)69440-3","article-title":"Human schistosomiasis","volume":"368","author":"Gryseels","year":"2006","journal-title":"Lancet (London England)"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1631-3","article-title":"Resolving the fibrotic niche of human liver cirrhosis at single-cell level","volume":"575","author":"Ramachandran","year":"2019","journal-title":"Nature"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-020-0736-z","article-title":"Single-cell transcriptome profiling reveals neutrophil heterogeneity in homeostasis and infection","volume":"21","author":"Xie","year":"2020","journal-title":"Nat Immunol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-020-0743-0","article-title":"Mapping systemic lupus erythematosus heterogeneity at the single-cell level","volume":"21","author":"Nehar-Belaid","year":"2020","journal-title":"Nat Immunol"},{"key":"B20","doi-asserted-by":"publisher","first-page":"1075","DOI":"10.1016\/j.immuni.2020.05.001","article-title":"Single-cell RNA sequencing of tumor-infiltrating NK cells reveals that inhibition of transcription factor HIF-1\u03b1 unleashes NK cell activity","volume":"52","author":"Ni","year":"2020","journal-title":"Immunity"},{"key":"B21","doi-asserted-by":"publisher","first-page":"829","DOI":"10.1016\/j.cell.2019.10.003","article-title":"Landscape and dynamics of single immune cells in hepatocellular carcinoma","volume":"179","author":"Zhang","year":"2019","journal-title":"Cell"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15023","article-title":"JQ1, a bromodomain inhibitor, suppresses Th17 effectors by blocking p300-mediated acetylation of ROR\u03b3t","volume":"177","author":"Wang","year":"2020","journal-title":"Br J Pharmacol"},{"key":"B23","doi-asserted-by":"publisher","first-page":"e16","DOI":"10.1093\/nar\/gky1173","article-title":"scFTD-seq: freeze-thaw lysis based, portable approach toward highly distributed single-cell 3' mRNA profiling","volume":"47","author":"Dura","year":"2019","journal-title":"Nucleic Acids Res"},{"key":"B24","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","article-title":"STAR: ultrafast universal RNA-seq aligner","volume":"29","author":"Dobin","year":"2013","journal-title":"Bioinformatics"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btt656","article-title":"featureCounts: an efficient general purpose program for assigning sequence reads to genomic features","volume":"30","author":"Liao","year":"2014","journal-title":"Bioinformatics"},{"key":"B26","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1038\/nbt.3192","article-title":"Spatial reconstruction of single-cell gene expression data","volume":"33","author":"Satija","year":"2015","journal-title":"Nat Biotechnol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.4096","article-title":"Integrating single-cell transcriptomic data across different conditions, technologies, and species","volume":"36","author":"Butler","year":"2018","journal-title":"Nat Biotechnol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1089\/omi.2011.0118","article-title":"clusterProfiler: an r package for comparing biological themes among gene clusters","volume":"16","author":"Yu","year":"2012","journal-title":"Omics"},{"key":"B29","doi-asserted-by":"publisher","first-page":"1088","DOI":"10.1038\/s41467-021-21246-9","article-title":"Inference and analysis of cell-cell communication using CellChat","volume":"12","author":"Jin","year":"2021","journal-title":"Nat Commun"},{"key":"B30","doi-asserted-by":"publisher","first-page":"109286","DOI":"10.1016\/j.celrep.2021.109286","article-title":"And transcriptome analysis after influenza infection reveals spatiotemporal dynamics of antigen-specific b cells","volume":"35","author":"Mathew","year":"2021","journal-title":"Cell Rep"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-020-00411-3","article-title":"Role of liver sinusoidal endothelial cells in liver diseases","volume":"18","author":"Gracia-Sancho","year":"2021","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"B32","doi-asserted-by":"publisher","first-page":"e966","DOI":"10.1371\/journal.pntd.0000966","article-title":"Quantifying quality of life and disability of patients with advanced schistosomiasis japonica","volume":"5","author":"Jia","year":"2011","journal-title":"PloS Negl Trop Dis"},{"key":"B33","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1016\/j.immuni.2019.05.014","article-title":"Single-cell RNA sequencing of the T helper cell response to house dust mites defines a distinct gene expression signature in airway Th2 cells","volume":"51","author":"Tibbitt","year":"2019","journal-title":"Immunity"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1038\/sj.icb.7100014","article-title":"Immunopathology of schistosomiasis","volume":"85","author":"Wilson","year":"2007","journal-title":"Immunol Cell Biol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.164.5.2585","article-title":"Schistosome infection of transgenic mice defines distinct and contrasting pathogenic roles for IL-4 and IL-13: IL-13 is a profibrotic agent","volume":"164","author":"Fallon","year":"2000","journal-title":"J Immunol (Baltimore Md. 1950)"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1003260","article-title":"IL-13 induces connective tissue growth factor in rat hepatic stellate cells via TGF-\u03b2-independent smad signaling","volume":"187","author":"Liu","year":"2011","journal-title":"J Immunol (Baltimore Md. 1950)"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1111\/imm.13288","article-title":"Hepatocyte CD1d protects against liver immunopathology in mice with schistosomiasis japonica","volume":"162","author":"Lei","year":"2021","journal-title":"Immunology"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.176.4.2476","article-title":"Activation of invariant NKT cells by the helminth parasite schistosoma mansoni","volume":"176","author":"Mallevaey","year":"2006","journal-title":"J Immunol (Baltimore Md. 1950)"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01178-06","article-title":"Invariant and noninvariant natural killer T cells exert opposite regulatory functions on the immune response during murine schistosomiasis","volume":"75","author":"Mallevaey","year":"2007","journal-title":"Infection Immun"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.00403","article-title":"Dual role of Fas\/FasL-mediated signal in peripheral immune tolerance","volume":"8","author":"Yamada","year":"2017","journal-title":"Front Immunol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.980872\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,22]],"date-time":"2022-12-22T11:03:17Z","timestamp":1671706997000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.980872\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,22]]},"references-count":40,"alternative-id":["10.3389\/fimmu.2022.980872"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2022.980872","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,22]]},"article-number":"980872"}}