{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T14:43:25Z","timestamp":1784299405659,"version":"3.55.0"},"reference-count":36,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2024,9,5]],"date-time":"2024-09-05T00:00:00Z","timestamp":1725494400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2024,9,5]],"date-time":"2024-09-05T00:00:00Z","timestamp":1725494400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Genes Immun"],"DOI":"10.1038\/s41435-024-00296-1","type":"journal-article","created":{"date-parts":[[2024,9,5]],"date-time":"2024-09-05T13:19:41Z","timestamp":1725542381000},"page":"423-433","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Integrated analyses reveal CST7 and DUSP5 regulate Th2 cells differentiation to promote chronic HBV infection"],"prefix":"10.1038","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5554-5735","authenticated-orcid":false,"given":"Gang","family":"Ning","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianxiang","family":"Liao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongye","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,9,5]]},"reference":[{"key":"296_CR1","doi-asserted-by":"publisher","first-page":"2308","DOI":"10.3389\/fimmu.2019.02308","volume":"10","author":"Z Ma","year":"2019","unstructured":"Ma Z, Zhang E, Gao S, Xiong Y, Lu M. Toward a functional cure for hepatitis B: The rationale and challenges for therapeutic targeting of the b cell immune response. Front Immunol. 2019;10:2308. https:\/\/doi.org\/10.3389\/fimmu.2019.02308.","journal-title":"Front Immunol"},{"key":"296_CR2","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1111\/apt.16659","volume":"55","author":"A Vittal","year":"2022","unstructured":"Vittal A, Sharma D, Hu A, Majeed NA, Terry N, Auh S, et al. Systematic review with meta-analysis: the impact of functional cure on clinical outcomes in patients with chronic hepatitis B. Aliment Pharm Ther. 2022;55:8\u201325. https:\/\/doi.org\/10.1111\/apt.16659.","journal-title":"Aliment Pharm Ther"},{"key":"296_CR3","doi-asserted-by":"publisher","first-page":"e0084","DOI":"10.1097\/HC9.0000000000000084","volume":"7","author":"WJ Jeng","year":"2023","unstructured":"Jeng WJ, Lok ASF. What will it take to cure hepatitis B? Hepatol Commun. 2023;7:e0084. https:\/\/doi.org\/10.1097\/HC9.0000000000000084.","journal-title":"Hepatol Commun"},{"key":"296_CR4","doi-asserted-by":"publisher","first-page":"1001","DOI":"10.1080\/14656566.2023.2211259","volume":"24","author":"N Khan","year":"2023","unstructured":"Khan N, Almajed MR, Fitzmaurice MG, Jafri SM. Developments in pharmacotherapeutic agents for hepatitis B\u2013how close are we to a functional cure? Expert Opin Pharmacother. 2023;24:1001\u201311. https:\/\/doi.org\/10.1080\/14656566.2023.2211259.","journal-title":"Expert Opin Pharmacother"},{"key":"296_CR5","doi-asserted-by":"publisher","DOI":"10.1038\/CDDIS.2015.42","volume":"6","author":"B Ye","year":"2015","unstructured":"Ye B, Liu X, Li X, Kong H, Tian L, Chen Y. T-cell exhaustion in chronic hepatitis B infection: current knowledge and clinical significance. Cell Death Dis. 2015;6:e1694. https:\/\/doi.org\/10.1038\/CDDIS.2015.42.","journal-title":"Cell Death Dis"},{"key":"296_CR6","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1080\/1744666X.2023.2198209","volume":"19","author":"E Allahmoradi","year":"2023","unstructured":"Allahmoradi E, Mohammadi R, Kheirandish Zarandi P, Alavian SM, Heiat M. The CD8+ T cell exhaustion mechanisms in chronic hepatitis B infection and immunotherapeutic strategies: a systematic review. Expert Rev Clin Immunol. 2023;19:671\u201388. https:\/\/doi.org\/10.1080\/1744666X.2023.2198209.","journal-title":"Expert Rev Clin Immunol"},{"key":"296_CR7","doi-asserted-by":"publisher","first-page":"616","DOI":"10.1016\/j.jhep.2009.12.017","volume":"52","author":"MK Maini","year":"2010","unstructured":"Maini MK, Schurich A. The molecular basis of the failed immune response in chronic HBV: Therapeutic implications. J Hepatol. 2010;52:616\u20139. https:\/\/doi.org\/10.1016\/j.jhep.2009.12.017.","journal-title":"J Hepatol"},{"key":"296_CR8","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1038\/s41575-020-0304-x","volume":"17","author":"P Ramachandran","year":"2020","unstructured":"Ramachandran P, Matchett KP, Dobie R, Wilson-Kanamori JR, Henderson NC. Single-cell technologies in hepatology: new insights into liver biology and disease pathogenesis. Nat Rev Gastroenterol Hepatol. 2020;17:457\u201372. https:\/\/doi.org\/10.1038\/s41575-020-0304-x.","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"296_CR9","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1038\/s41586-019-1373-2","volume":"572","author":"N Aizarani","year":"2019","unstructured":"Aizarani N, Saviano A, Sagar, Mailly L, Durand S, Herman JS, et al. A human liver cell atlas reveals heterogeneity and epithelial progenitors. Nature. 2019;572:199\u2013204.https:\/\/doi.org\/10.1038\/s41586-019-1373-2.","journal-title":"Nature"},{"key":"296_CR10","doi-asserted-by":"publisher","first-page":"1632","DOI":"10.1111\/liv.13427","volume":"37","author":"W Zhou","year":"2017","unstructured":"Zhou W, Ma Y, Zhang J, Hu J, Zhang M, Wang Y, et al. Predictive model for inflammation grades of chronic hepatitis B: Large-scale analysis of clinical parameters and gene expressions. Liver Int. 2017;37:1632\u201341. https:\/\/doi.org\/10.1111\/liv.13427.","journal-title":"Liver Int"},{"key":"296_CR11","doi-asserted-by":"publisher","DOI":"10.1038\/srep43446","volume":"7","author":"M Wang","year":"2017","unstructured":"Wang M, Gong Q, Zhang J, Chen L, Zhang Z, Lu L, et al. Characterization of gene expression profiles in HBV-related liver fibrosis patients and identification of ITGBL1 as a key regulator of fibrogenesis. Sci Rep. 2017;7:43446. https:\/\/doi.org\/10.1038\/srep43446.","journal-title":"Sci Rep"},{"key":"296_CR12","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1136\/gutjnl-2021-325915","volume":"72","author":"C Zhang","year":"2023","unstructured":"Zhang C, Li J, Cheng Y, Meng F, Song JW, Fan X, et al. Single-cell RNA sequencing reveals intrahepatic and peripheral immune characteristics related to disease phases in HBV-infected patients. Gut. 2023;72:153\u201367. https:\/\/doi.org\/10.1136\/gutjnl-2021-325915.","journal-title":"Gut"},{"key":"296_CR13","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-9-559","volume":"9","author":"P Langfelder","year":"2008","unstructured":"Langfelder P, Horvath S. WGCNA: An R package for weighted correlation network analysis. BMC Bioinforma. 2008;9:559. https:\/\/doi.org\/10.1186\/1471-2105-9-559.","journal-title":"BMC Bioinforma"},{"key":"296_CR14","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-14-7","volume":"14","author":"S H\u00e4nzelmann","year":"2013","unstructured":"H\u00e4nzelmann S, Castelo R, Guinney J. GSVA: Gene set variation analysis for microarray and RNA-Seq data. BMC Bioinforma. 2013;14:7. https:\/\/doi.org\/10.1186\/1471-2105-14-7.","journal-title":"BMC Bioinforma"},{"key":"296_CR15","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-017-1349-1","volume":"18","author":"D Aran","year":"2017","unstructured":"Aran D, Hu Z, Butte AJ. xCell: Digitally portraying the tissue cellular heterogeneity landscape. Genome Biol. 2017;18:220. https:\/\/doi.org\/10.1186\/s13059-017-1349-1.","journal-title":"Genome Biol"},{"key":"296_CR16","doi-asserted-by":"publisher","first-page":"1289","DOI":"10.1038\/s41592-019-0619-0","volume":"16","author":"I Korsunsky","year":"2019","unstructured":"Korsunsky I, Millard N, Fan J, Slowikowski K, Zhang F, Wei K, et al. Fast, sensitive and accurate integration of single-cell data with Harmony. Nat Methods. 2019;16:1289\u201396. https:\/\/doi.org\/10.1038\/s41592-019-0619-0.","journal-title":"Nat Methods"},{"key":"296_CR17","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1038\/s41592-019-0466-z","volume":"16","author":"N Barkas","year":"2019","unstructured":"Barkas N, Petukhov V, Nikolaeva D, Lozinsky Y, Demharter S, Khodosevich K, et al. Joint analysis of heterogeneous single-cell RNA-seq dataset collections. Nat Methods. 2019;16:695\u20138. https:\/\/doi.org\/10.1038\/s41592-019-0466-z.","journal-title":"Nat Methods"},{"key":"296_CR18","doi-asserted-by":"publisher","first-page":"1071","DOI":"10.1111\/jvh.13319","volume":"27","author":"G Ning","year":"2020","unstructured":"Ning G, Zhen L-M, Xu W-X, Li X-J, Wu L-N, Liu Y, et al. Suppression of complement component 2 expression by hepatitis B virus contributes to the viral persistence in chronic hepatitis B patients. J Viral Hepat. 2020;27:1071\u201381. https:\/\/doi.org\/10.1111\/jvh.13319.","journal-title":"J Viral Hepat"},{"key":"296_CR19","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1146\/annurev.iy.11.040193.003035","volume":"11","author":"MA Farrar","year":"1993","unstructured":"Farrar MA, Schreiber RD. The molecular cell biology of interferon-\u03b3 and its receptor. Annu Rev Immunol. 1993;11:571\u2013611. https:\/\/doi.org\/10.1146\/annurev.iy.11.040193.003035.","journal-title":"Annu Rev Immunol"},{"key":"296_CR20","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1186\/s12865-019-0309-9","volume":"20","author":"Y Dong","year":"2019","unstructured":"Dong Y, Li X, Zhang L, Zhu Q, Chen C, Bao J, et al. CD4+ T cell exhaustion revealed by high PD-1 and LAG-3 expression and the loss of helper T cell function in chronic hepatitis B. BMC Immunol. 2019;20:27. https:\/\/doi.org\/10.1186\/s12865-019-0309-9.","journal-title":"BMC Immunol"},{"key":"296_CR21","doi-asserted-by":"publisher","first-page":"1273","DOI":"10.1084\/jem.180.4.1273","volume":"180","author":"MB Graham","year":"1994","unstructured":"Graham MB, Braciale VL, Braciale TJ. Influenza virus-specific CD4+ T helper type 2 T lymphocytes do not promote recovery from experimental virus infection. J Exp Med. 1994;180:1273\u201382. https:\/\/doi.org\/10.1084\/jem.180.4.1273.","journal-title":"J Exp Med"},{"key":"296_CR22","doi-asserted-by":"publisher","first-page":"5230","DOI":"10.1128\/jvi.70.8.5230-5235.1996","volume":"70","author":"TM Moran","year":"1996","unstructured":"Moran TM, Isobe H, Fernandez-Sesma A, Schulman JL. Interleukin-4 causes delayed virus clearance in influenza virus-infected mice. J Virol. 1996;70:5230\u20135. https:\/\/doi.org\/10.1128\/jvi.70.8.5230-5235.1996.","journal-title":"J Virol"},{"key":"296_CR23","doi-asserted-by":"publisher","first-page":"2192","DOI":"10.1128\/jvi.71.3.2192-2201.1997","volume":"71","author":"DR Milich","year":"1997","unstructured":"Milich DR, Sch\u00f6del F, Hughes JL, Jones JE, Peterson DL. The hepatitis B virus core and e antigens elicit different Th cell subsets: antigen structure can affect Th cell phenotype. J Virol. 1997;71:2192\u2013201. https:\/\/doi.org\/10.1128\/jvi.71.3.2192-2201.1997.","journal-title":"J Virol"},{"key":"296_CR24","first-page":"584","volume":"21","author":"YP Han","year":"2013","unstructured":"Han YP, Li J, Jiang LF, Xu QQ, Liu B, Dong L, et al. [Hepatitis B e antigen from chronic hepatitis B patients induces Th1\/Th2 cytokine imbalance in vitro]. Zhonghua Gan Zang Bing Za Zhi. 2013;21:584\u20139.","journal-title":"Zhonghua Gan Zang Bing Za Zhi"},{"key":"296_CR25","doi-asserted-by":"publisher","first-page":"3088","DOI":"10.4049\/jimmunol.162.5.3088","volume":"162","author":"BD Livingston","year":"1999","unstructured":"Livingston BD, Alexander J, Crimi C, Oseroff C, Celis E, Daly K, et al. Altered Helper T Lymphocyte Function Associated with Chronic Hepatitis B Virus Infection and its Role in Response to Therapeutic Vaccination in Humans. J Immunol. 1999;162:3088\u201395. https:\/\/doi.org\/10.4049\/jimmunol.162.5.3088.","journal-title":"J Immunol"},{"key":"296_CR26","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1038\/nri.2017.118","volume":"18","author":"JA Walker","year":"2018","unstructured":"Walker JA, McKenzie ANJ. TH2 cell development and function. Nat Rev Immunol. 2018;18:121\u201333. https:\/\/doi.org\/10.1038\/nri.2017.118.","journal-title":"Nat Rev Immunol"},{"key":"296_CR27","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1016\/j.cmet.2016.12.011","volume":"25","author":"EH Ma","year":"2017","unstructured":"Ma EH, Bantug G, Griss T, Condotta S, Johnson RM, Samborska B, et al. Serine Is an Essential Metabolite for Effector T Cell Expansion. Cell Metab. 2017;25:345\u201357. https:\/\/doi.org\/10.1016\/j.cmet.2016.12.011.","journal-title":"Cell Metab"},{"key":"296_CR28","doi-asserted-by":"publisher","first-page":"57","DOI":"10.2478\/raon-2019-0007","volume":"53","author":"M Prunk","year":"2019","unstructured":"Prunk M, Nanut MP, Sabotic J, Svajger U, Kos J. Increased cystatin F levels correlate with decreased cytotoxicity of cytotoxic T cells. Radio Oncol. 2019;53:57\u201368. https:\/\/doi.org\/10.2478\/raon-2019-0007.","journal-title":"Radio Oncol"},{"key":"296_CR29","doi-asserted-by":"publisher","first-page":"1051","DOI":"10.1007\/s13402-021-00618-9","volume":"44","author":"E Senjor","year":"2021","unstructured":"Senjor E, Peri\u0161i\u0107 Nanut M, Breznik B, Mitrovi\u0107 A, Mlakar J, Rotter A, et al. Cystatin F acts as a mediator of immune suppression in glioblastoma. Cell Oncol. 2021;44:1051\u201363. https:\/\/doi.org\/10.1007\/s13402-021-00618-9.","journal-title":"Cell Oncol"},{"key":"296_CR30","doi-asserted-by":"publisher","first-page":"8408","DOI":"10.3390\/ijms22168408","volume":"22","author":"MP Nanut","year":"2021","unstructured":"Nanut MP, Pawelec G, Kos J. Human CD4+ T-cell clone expansion leads to the expression of the cysteine peptidase inhibitor cystatin F. Int J Mol Sci. 2021;22:8408. https:\/\/doi.org\/10.3390\/ijms22168408.","journal-title":"Int J Mol Sci"},{"key":"296_CR31","doi-asserted-by":"publisher","first-page":"119321","DOI":"10.1016\/j.bbamcr.2022.119321","volume":"1869","author":"R Jarou\u0161ek","year":"2022","unstructured":"Jarou\u0161ek R, Mikulov\u00e1 A, Da\u010fov\u00e1 P, Tau\u0161 P, Kurucov\u00e1 T, Plevov\u00e1 K, et al. Single-cell RNA sequencing analysis of T helper cell differentiation and heterogeneity. Biochim Biophys Acta Mol Cell Res. 2022;1869:119321. https:\/\/doi.org\/10.1016\/j.bbamcr.2022.119321.","journal-title":"Biochim Biophys Acta Mol Cell Res"},{"key":"296_CR32","doi-asserted-by":"publisher","first-page":"1433","DOI":"10.3390\/cells8111433","volume":"8","author":"HC Chuang","year":"2019","unstructured":"Chuang HC, Tan TH. Map4k family kinases and dusp family phosphatases in t-cell signaling and systemic lupus erythematosus. Cells. 2019;8:1433. https:\/\/doi.org\/10.3390\/cells8111433.","journal-title":"Cells"},{"key":"296_CR33","doi-asserted-by":"publisher","first-page":"e0167246","DOI":"10.1371\/journal.pone.0167246","volume":"11","author":"RG Kutty","year":"2016","unstructured":"Kutty RG, Xin G, Schauder DM, Cossette SM, Bordas M, Cui W, et al. Dual specificity phosphatase 5 is essential for T cell survival. PLoS One. 2016;11:e0167246. https:\/\/doi.org\/10.1371\/journal.pone.0167246.","journal-title":"PLoS One"},{"key":"296_CR34","doi-asserted-by":"publisher","first-page":"631879","DOI":"10.3389\/fphar.2021.631879","volume":"12","author":"S Goel","year":"2021","unstructured":"Goel S, Saheb Sharif-Askari F, Saheb Sharif Askari N, Madkhana B, Alwaa AM, Mahboub B, et al. SARS-CoV-2 Switches \u2018on\u2019 MAPK and NF\u03baB Signaling via the Reduction of Nuclear DUSP1 and DUSP5 Expression. Front Pharm. 2021;12:631879. https:\/\/doi.org\/10.3389\/fphar.2021.631879.","journal-title":"Front Pharm"},{"key":"296_CR35","doi-asserted-by":"publisher","first-page":"218","DOI":"10.15252\/embj.201489456","volume":"34","author":"DA Holmes","year":"2015","unstructured":"Holmes DA, Yeh J, Yan D, Xu M, Chan AC. Dusp5 negatively regulates IL \u201033\u2010mediated eosinophil survival and function. EMBO J. 2015;34:218\u201335. https:\/\/doi.org\/10.15252\/embj.201489456.","journal-title":"EMBO J"},{"key":"296_CR36","doi-asserted-by":"publisher","first-page":"3083","DOI":"10.1002\/art.38787","volume":"66","author":"SJ Moon","year":"2014","unstructured":"Moon SJ, Lim MA, Park JS, Byun JK, Kim SM, Park MK, et al. Dual-specificity phosphatase 5 attenuates autoimmune arthritis in mice via reciprocal regulation of the Th17\/Treg cell balance and inhibition of osteoclastogenesis. Arthritis Rheumatol. 2014;66:3083\u201395. https:\/\/doi.org\/10.1002\/art.38787.","journal-title":"Arthritis Rheumatol"}],"container-title":["Genes & Immunity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41435-024-00296-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41435-024-00296-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41435-024-00296-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,15]],"date-time":"2024-10-15T15:10:37Z","timestamp":1729005037000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41435-024-00296-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,5]]},"references-count":36,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2024,10]]}},"alternative-id":["296"],"URL":"https:\/\/doi.org\/10.1038\/s41435-024-00296-1","relation":{},"ISSN":["1476-5470"],"issn-type":[{"value":"1476-5470","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,5]]},"assertion":[{"value":"6 June 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 August 2024","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 August 2024","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 September 2024","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"The study was conducted in compliance with the Declaration of Helsinki and its subsequent amendments. Written consents had already been obtained before our study. Besides, the research protocol received approval from the Ethics Committee of Guangzhou First People\u2019s Hospital, affiliated with the South China University of Technology. All data and methodologies used in our study adhere to legal and ethical standards, and comply with all applicable ethical principles and research ethics review regulations.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}}]}}