{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:46:06Z","timestamp":1760060766593,"version":"build-2065373602"},"reference-count":75,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T00:00:00Z","timestamp":1759968000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Jiangsu Preventive Medicine Association","award":["Ym2023054","K2023042","Y20222028","ZDXYS202207"],"award-info":[{"award-number":["Ym2023054","K2023042","Y20222028","ZDXYS202207"]}]},{"name":"Key Projects of Jiangsu Provincial Health Commission","award":["Ym2023054","K2023042","Y20222028","ZDXYS202207"],"award-info":[{"award-number":["Ym2023054","K2023042","Y20222028","ZDXYS202207"]}]},{"name":"Wuxi Science and Technology Research Project (Medical and Health Technology Research)","award":["Ym2023054","K2023042","Y20222028","ZDXYS202207"],"award-info":[{"award-number":["Ym2023054","K2023042","Y20222028","ZDXYS202207"]}]},{"name":"Jiangsu Province Capability Improvement Project through Science, Technology, and Education","award":["Ym2023054","K2023042","Y20222028","ZDXYS202207"],"award-info":[{"award-number":["Ym2023054","K2023042","Y20222028","ZDXYS202207"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>To further investigate the role of PKC\u03bb\/\u03b9 in Schistosoma japonicum-induced hepatic fibrosis, we employed a CD4+ T-cell-specific PKC\u03bb\/\u03b9 conditional knockout (KOSJ) mouse model, with wild-type (WTSJ) mice used as controls. Transcriptomic profiling of hepatic mRNA was used to reveal the immune regulatory mechanisms underlying the role of PKC\u03bb\/\u03b9 in the hepatic fibrosis caused by S. japonicum infection. Flow cytometry, RT\u2013qPCR and ELISA were used to analyze the effects of PKC\u03bb\/\u03b9 on Tfh and Tfr cells, and single-cell RNA sequencing was used to elucidate the interactions between Tfr and B cells. The results showed that PKC\u03bb\/\u03b9 deficiency led to altered BCR signaling gene expression, reduced germinal center activity, and decreased anti-SEA antibody levels. Tfh cells and key factors including IL-21, CXCR5, and ICOS were downregulated, while Tfr cells and IL-10+ B cells increased. Additionally, hepatic neutrophils decreased and Treg\/Tfr ratios rose, with enhanced IL-10-mediated cellular crosstalk. These findings indicate that PKC\u03bb\/\u03b9 deficiency attenuates liver fibrosis by inhibiting Tfh differentiation, promoting Tfr function, and activating IL-10-producing Breg cells, suggesting its potential as a therapeutic target.<\/jats:p>","DOI":"10.3390\/biom15101430","type":"journal-article","created":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:54:31Z","timestamp":1760028871000},"page":"1430","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Conditional Ablation of PKC\u03bb\/\u03b9 in CD4+ T Cells Ameliorates Hepatic Fibrosis in Schistosoma japonicum-Infected Mice via T Follicular Helper (Tfh) Cell Suppression Coupled with Increased Follicular Regulatory T (Tfr) and Regulatory B (Breg) Cell Activities"],"prefix":"10.3390","volume":"15","author":[{"given":"Congjin","family":"Mei","sequence":"first","affiliation":[{"name":"National Health Commission Key Laboratory of Parasitic Disease Control and Prevention, Jiangsu Provincial Key Laboratory on Parasite and Vector Control Technology, Jiangsu Institute of Parasitic Diseases, Wuxi 214064, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yingying","family":"Yang","sequence":"additional","affiliation":[{"name":"National Health Commission Key Laboratory of Parasitic Disease Control and Prevention, Jiangsu Provincial Key Laboratory on Parasite and Vector Control Technology, Jiangsu Institute of Parasitic Diseases, Wuxi 214064, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Panpan","family":"Dong","sequence":"additional","affiliation":[{"name":"National Health Commission Key Laboratory of Parasitic Disease Control and Prevention, Jiangsu Provincial Key Laboratory on Parasite and Vector Control Technology, Jiangsu Institute of Parasitic Diseases, Wuxi 214064, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julu","family":"Lu","sequence":"additional","affiliation":[{"name":"National Health Commission Key Laboratory of Parasitic Disease Control and Prevention, Jiangsu Provincial Key Laboratory on Parasite and Vector Control Technology, Jiangsu Institute of Parasitic Diseases, Wuxi 214064, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinyue","family":"Zhang","sequence":"additional","affiliation":[{"name":"National Health Commission Key Laboratory of Parasitic Disease Control and Prevention, Jiangsu Provincial Key Laboratory on Parasite and Vector Control Technology, Jiangsu Institute of Parasitic Diseases, Wuxi 214064, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingping","family":"Li","sequence":"additional","affiliation":[{"name":"National Health Commission Key Laboratory of Parasitic Disease Control and Prevention, Jiangsu Provincial Key Laboratory on Parasite and Vector Control Technology, Jiangsu Institute of Parasitic Diseases, Wuxi 214064, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3897-5925","authenticated-orcid":false,"given":"Lijun","family":"Song","sequence":"additional","affiliation":[{"name":"National Health Commission Key Laboratory of Parasitic Disease Control and Prevention, Jiangsu Provincial Key Laboratory on Parasite and Vector Control Technology, Jiangsu Institute of Parasitic Diseases, Wuxi 214064, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chuanxin","family":"Yu","sequence":"additional","affiliation":[{"name":"National Health Commission Key Laboratory of Parasitic Disease Control and Prevention, Jiangsu Provincial Key Laboratory on Parasite and Vector Control Technology, Jiangsu Institute of Parasitic Diseases, Wuxi 214064, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e327","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":"ref_2","doi-asserted-by":"crossref","unstructured":"Qiu, S., Fan, X., Yang, Y., Dong, P., Zhou, W., Xu, Y., Zhou, Y., Guo, F., Zheng, Y., and Yang, J.Q. (2017). Schistosoma japonicum infection downregulates house dust mite-induced allergic airway inflammation in mice. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0179565"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Schwartz, C., and Fallon, P.G. (2018). Schistosoma \u201cEggs-Iting\u201d the Host: Granuloma Formation and Egg Excretion. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.02492"},{"key":"ref_4","doi-asserted-by":"crossref","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":"ref_5","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1038\/sj.icb.7100014","article-title":"Immunopathology of schistosomiasis","volume":"85","author":"Wilson","year":"2007","journal-title":"Immunol. Cell Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1358","DOI":"10.1126\/science.1064462","article-title":"Modulation of blood fluke development in the liver by hepatic CD4+ lymphocytes","volume":"294","author":"Davies","year":"2001","journal-title":"Science"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Zheng, B., Zhang, J., Chen, H., Nie, H., Miller, H., Gong, Q., and Liu, C. (2020). T Lymphocyte-Mediated Liver Immunopathology of Schistosomiasis. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.00061"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1093\/infdis\/139.6.659","article-title":"Factors in the pathogenesis of acute schistosomiasis mansoni","volume":"139","author":"Hiatt","year":"1979","journal-title":"J. Infect. Dis."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Carson, J.P., and Gobert, G.N. (2021). Modulation of the Host Immune Response by Schistosome Egg-Secreted Proteins Is a Critical Avenue of Host-Parasite Communication. Pathogens, 10.","DOI":"10.3390\/pathogens10070863"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2585","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."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"82","DOI":"10.4049\/jimmunol.2200301","article-title":"Longitudinal Immune Profiling Highlights CD4+ T Cell Exhaustion Correlated with Liver Fibrosis in Schistosoma japonicum Infection","volume":"210","author":"Ren","year":"2023","journal-title":"J. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1186\/s13071-020-04015-3","article-title":"B cells induced by Schistosoma japonicum infection display diverse regulatory phenotypes and modulate CD4(+) T cell response","volume":"13","author":"Xiao","year":"2020","journal-title":"Parasit. Vectors"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1084\/jem.187.4.619","article-title":"CD4+ T cell-mediated granulomatous pathology in schistosomiasis is downregulated by a B cell-dependent mechanism requiring Fc receptor signaling","volume":"187","author":"Jankovic","year":"1998","journal-title":"J. Exp. Med."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Ji, F., Liu, Z., Cao, J., Li, N., Liu, Z., Zuo, J., Chen, Y., Wang, X., and Sun, J. (2008). B cell response is required for granuloma formation in the early infection of Schistosoma japonicum. PLoS ONE, 3.","DOI":"10.1371\/journal.pone.0001724"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.it.2010.11.005","article-title":"To B or not to B: B cells and the Th2-type immune response to helminths","volume":"32","author":"Harris","year":"2011","journal-title":"Trends Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1084\/jem.20021290","article-title":"Costimulation via OX40L expressed by B cells is sufficient to determine the extent of primary CD4 cell expansion and Th2 cytokine secretion in vivo","volume":"197","author":"Linton","year":"2003","journal-title":"J. Exp. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1128\/IAI.70.2.812-819.2002","article-title":"Fas ligand-expressing B-1a lymphocytes mediate CD4(+)-T-cell apoptosis during schistosomal infection: Induction by interleukin 4 (IL-4) and IL-10","volume":"70","author":"Lundy","year":"2002","journal-title":"Infect. Immun."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"6346","DOI":"10.4049\/jimmunol.173.10.6346","article-title":"Helminth infection protects mice from anaphylaxis via IL-10-producing B cells","volume":"173","author":"Mangan","year":"2004","journal-title":"J. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1084\/jem.20102065","article-title":"B cell priming for extrafollicular antibody responses requires Bcl-6 expression by T cells","volume":"208","author":"Lee","year":"2011","journal-title":"J. Exp. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1038\/ni.3554","article-title":"TFH cells progressively differentiate to regulate the germinal center response","volume":"17","author":"Weinstein","year":"2016","journal-title":"Nat. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1038\/82717","article-title":"Reciprocal regulation of polarized cytokine production by effector B and T cells","volume":"1","author":"Harris","year":"2000","journal-title":"Nat. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1016\/j.immuni.2011.03.023","article-title":"ICOS receptor instructs T follicular helper cell versus effector cell differentiation via induction of the transcriptional repressor Bcl6","volume":"34","author":"Choi","year":"2011","journal-title":"Immunity"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1038\/nature13803","article-title":"T-B-cell entanglement and ICOSL-driven feed-forward regulation of germinal centre reaction","volume":"517","author":"Liu","year":"2015","journal-title":"Nature"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Chen, X., Yang, X., Li, Y., Zhu, J., Zhou, S., Xu, Z., He, L., Xue, X., Zhang, W., and Dong, X. (2014). Follicular helper T cells promote liver pathology in mice during Schistosoma japonicum infection. PLoS Pathog., 10.","DOI":"10.1371\/journal.ppat.1004097"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1111\/j.1600-065X.2012.01121.x","article-title":"T-follicular helper cell differentiation and the co-option of this pathway by non-helper cells","volume":"247","author":"Linterman","year":"2012","journal-title":"Immunol. Rev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1084\/jem.20062512","article-title":"Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression","volume":"204","author":"Deaglio","year":"2007","journal-title":"J. Exp. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1038\/ni.2496","article-title":"The receptor PD-1 controls follicular regulatory T cells in the lymph nodes and blood","volume":"14","author":"Sage","year":"2013","journal-title":"Nat. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Ding, T., Su, R., Wu, R., Xue, H., Wang, Y., Su, R., Gao, C., Li, X., and Wang, C. (2021). Frontiers of Autoantibodies in Autoimmune Disorders: Crosstalk Between Tfh\/Tfr and Regulatory B Cells. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.641013"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"He, S., Li, Q., Huang, Q., and Cheng, J. (2022). Targeting Protein Kinase C for Cancer Therapy. Cancer, 14.","DOI":"10.3390\/cancers14051104"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1038\/sj.cdd.4401823","article-title":"PKCzeta at the crossroad of NF-kappaB and Jak1\/Stat6 signaling pathways","volume":"13","author":"Moscat","year":"2006","journal-title":"Cell Death Differ."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"109071","DOI":"10.1016\/j.clim.2022.109071","article-title":"The role of protein kinase C isoenzymes in the pathogenesis of human autoimmune diseases","volume":"241","author":"Sipka","year":"2022","journal-title":"Clin. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1002\/j.1460-2075.1996.tb00414.x","article-title":"EGF or PDGF receptors activate atypical PKClambda through phosphatidylinositol 3-kinase","volume":"15","author":"Akimoto","year":"1996","journal-title":"Embo J."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1093\/jb\/mvg018","article-title":"Protein kinase C lambda\/iota (PKClambda\/iota): A PKC isotype essential for the development of multicellular organisms","volume":"133","author":"Suzuki","year":"2003","journal-title":"J. Biochem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1073\/pnas.0805907106","article-title":"Loss of PKC lambda\/iota impairs Th2 establishment and allergic airway inflammation in vivo","volume":"106","author":"Yang","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1016\/j.bbadis.2018.01.001","article-title":"PKClambda\/iota regulates Th17 differentiation and house dust mite-induced allergic airway inflammation","volume":"1864","author":"Yang","year":"2018","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Wang, Y., Lin, C., Cao, Y., Duan, Z., Guan, Z., Xu, J., Zhu, X.Q., and Xia, C. (2017). Up-regulation of Interleukin-21 Contributes to Liver Pathology of Schistosomiasis by Driving GC Immune Responses and Activating HSCs in Mice. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-16783-7"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/j.immuni.2014.10.004","article-title":"T follicular helper cell differentiation, function, and roles in disease","volume":"41","author":"Crotty","year":"2014","journal-title":"Immunity"},{"key":"ref_38","unstructured":"(2008). Laboratories - General requirements for biosafety (Standard No. GB19489-2008)."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Zhu, Y., Hua, W., Xu, M., He, W., Wang, X., Dai, Y., Zhao, S., Tang, J., Wang, S., and Lu, S. (2012). A novel immunodiagnostic assay to detect serum antibody response against selected soluble egg antigen fractions from Schistosoma japonicum. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0044032"},{"key":"ref_40","first-page":"291","article-title":"Quantification of histochemical staining by color deconvolution","volume":"23","author":"Ruifrok","year":"2001","journal-title":"Anal. Quant. Cytol. Histol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/nmeth.2019","article-title":"Fiji: An open-source platform for biological-image analysis","volume":"9","author":"Schindelin","year":"2012","journal-title":"Nat. Methods"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Tan, K., Deng, J., Liu, Y., Zhang, Y., Xiong, Y., Yuan, S., Liu, J., Chen, Z., Liu, Y., and Cao, W. (2025). Yiqi Juanshen decoction alleviates renal interstitial fibrosis by targeting the LOXL2\/PI3K\/AKT pathway to suppress EMT and inflammation. Sci. Rep., 15.","DOI":"10.1038\/s41598-025-86622-7"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1146\/annurev.immunol.021908.132641","article-title":"Regulation and function of NF-kappaB transcription factors in the immune system","volume":"27","author":"Vallabhapurapu","year":"2009","journal-title":"Annu. Rev. Immunol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e20201811","DOI":"10.1084\/jem.20201811","article-title":"LILRB4 suppresses immunity in solid tumors and is a potential target for immunotherapy","volume":"218","author":"Sharma","year":"2021","journal-title":"J. Exp. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1038\/nri2206","article-title":"Fcgamma receptors as regulators of immune responses","volume":"8","author":"Nimmerjahn","year":"2008","journal-title":"Nat. Rev. Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"44315","DOI":"10.1074\/jbc.M105446200","article-title":"CD22 regulates B cell receptor-mediated signals via two domains that independently recruit Grb2 and SHP-1","volume":"276","author":"Otipoby","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2911","DOI":"10.1007\/s00436-015-4492-1","article-title":"Interleukin-33 promotes Th2 immune responses in infected mice with Schistosoma japonicum","volume":"114","author":"Yu","year":"2015","journal-title":"Parasitol. Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1186\/s13071-022-05283-x","article-title":"Deficiency of PKClambda\/iota alleviates the liver pathologic impairment of Schistosoma japonicum infection by thwarting Th2 response","volume":"15","author":"Mei","year":"2022","journal-title":"Parasit. Vectors"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1046\/j.1365-3083.1998.00376.x","article-title":"Infection of B-cell-deficient mice by the parasite Schistosoma mansoni: Demonstration of the participation of B cells in granuloma modulation","volume":"48","author":"Ferru","year":"1998","journal-title":"Scand. J. Immunol."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Yong, L., Tang, Y., Ren, C., Liu, M., Shen, J., and Hou, X. (2019). B1 cells protect against Schistosoma japonicum-induced liver inflammation and fibrosis by controlling monocyte infiltration. PLoS Negl. Trop. Dis., 13.","DOI":"10.1371\/journal.pntd.0007474"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2092","DOI":"10.1016\/j.ymthe.2022.03.016","article-title":"Host liver-derived extracellular vesicles deliver miR-142a-3p induces neutrophil extracellular traps via targeting WASL to block the development of Schistosoma japonicum","volume":"30","author":"Wang","year":"2022","journal-title":"Mol. Ther."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Haeberlein, S., Obieglo, K., Ozir-Fazalalikhan, A., Chaye, M.A.M., Veninga, H., van der Vlugt, L., Voskamp, A., Boon, L., den Haan, J.M.M., and Westerhof, L.B. (2017). Schistosome egg antigens, including the glycoprotein IPSE\/alpha-1, trigger the development of regulatory B cells. PLoS Pathog., 13.","DOI":"10.1371\/journal.ppat.1006539"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1084\/jem.20111174","article-title":"STAT5 is a potent negative regulator of TFH cell differentiation","volume":"209","author":"Johnston","year":"2012","journal-title":"J. Exp. Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2089","DOI":"10.4049\/jimmunol.1101393","article-title":"Cutting Edge: Distinct waves of BCL6 expression during T follicular helper cell development","volume":"187","author":"Baumjohann","year":"2011","journal-title":"J. Immunol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"4014","DOI":"10.4049\/jimmunol.1202963","article-title":"Bcl6 expressing follicular helper CD4 T cells are fate committed early and have the capacity to form memory","volume":"190","author":"Choi","year":"2013","journal-title":"J. Immunol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1126\/science.1175870","article-title":"Bcl6 and Blimp-1 are reciprocal and antagonistic regulators of T follicular helper cell differentiation","volume":"325","author":"Johnston","year":"2009","journal-title":"Science"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2049","DOI":"10.1084\/jem.20111504","article-title":"B and T cells collaborate in antiviral responses via IL-6, IL-21, and transcriptional activator and coactivator, Oct2 and OBF-1","volume":"209","author":"Karnowski","year":"2012","journal-title":"J. Exp. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1146\/annurev-immunol-041015-055605","article-title":"Follicular Helper T Cells","volume":"34","author":"Vinuesa","year":"2016","journal-title":"Annu. Rev. Immunol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"14647","DOI":"10.1038\/ncomms14647","article-title":"IL-21 restricts T follicular regulatory T cell proliferation through Bcl-6 mediated inhibition of responsiveness to IL-2","volume":"8","author":"Jandl","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1775","DOI":"10.1016\/j.cell.2021.02.027","article-title":"Follicular regulatory T cells produce neuritin to regulate B cells","volume":"184","author":"Roco","year":"2021","journal-title":"Cell"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1016\/j.immuni.2019.04.011","article-title":"T Follicular Helper Cell Biology: A Decade of Discovery and Diseases","volume":"50","author":"Crotty","year":"2019","journal-title":"Immunity"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1084\/jem.20090303","article-title":"T follicular helper cells differentiate from Th2 cells in response to helminth antigens","volume":"206","author":"Taylor","year":"2009","journal-title":"J. Exp. Med."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"5191","DOI":"10.1172\/JCI76861","article-title":"Circulating T follicular regulatory and helper cells have memory-like properties","volume":"124","author":"Sage","year":"2014","journal-title":"J. Clin. Investig."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1038\/ni.1837","article-title":"Effectors and memories: Bcl-6 and Blimp-1 in T and B lymphocyte differentiation","volume":"11","author":"Crotty","year":"2010","journal-title":"Nat. Immunol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"107575","DOI":"10.1016\/j.celrep.2020.107575","article-title":"Control of Germinal Center Localization and Lineage Stability of Follicular Regulatory T Cells by the Blimp1 Transcription Factor","volume":"31","author":"Shen","year":"2020","journal-title":"Cell Rep."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1189\/jlb.1212653","article-title":"Spatial and temporal transcriptomics of Schistosoma japonicum-induced hepatic granuloma formation reveals novel roles for neutrophils","volume":"94","author":"Chuah","year":"2013","journal-title":"J. Leukoc. Biol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1186\/s13071-022-05201-1","article-title":"Inhibition of COX-2 ameliorates murine liver schistosomiasis japonica through splenic cellular immunoregulation","volume":"15","author":"Qi","year":"2022","journal-title":"Parasit. Vectors"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1186\/s13071-017-2538-1","article-title":"Dynamic expression of cytokine and transcription factor genes during experimental Fasciola gigantica infection in buffaloes","volume":"10","author":"Shi","year":"2017","journal-title":"Parasit. Vectors"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"907","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."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1666","DOI":"10.1111\/cmi.12316","article-title":"Defining a pro-inflammatory neutrophil phenotype in response to schistosome eggs","volume":"16","author":"Chuah","year":"2014","journal-title":"Cell Microbiol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1016\/j.jaci.2010.03.024","article-title":"Regulatory B cells that produce IL-10: A breath of fresh air in allergic airway disease","volume":"125","author":"Tedder","year":"2011","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Chaye, M.A.M., Gasan, T.A., Ozir-Fazalalikhan, A., Scheenstra, M.R., Zawistowska-Deniziak, A., van Hengel, O.R.J., Gentenaar, M., Manurung, M.D., Harvey, M.R., and Codee, J.D.C. (2023). Schistosoma mansoni egg-derived thioredoxin and Sm14 drive the development of IL-10 producing regulatory B cells. PLoS Negl. Trop. Dis., 17.","DOI":"10.1371\/journal.pntd.0011344"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"607","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":"ref_74","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1016\/j.imbio.2010.12.003","article-title":"IL-10 controls Th2-type cytokine production and eosinophil infiltration in a mouse model of allergic airway inflammation","volume":"216","author":"Kosaka","year":"2011","journal-title":"Immunobiology"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1038\/mi.2015.66","article-title":"Induction of human IL-10-producing neutrophils by LPS-stimulated Treg cells and IL-10","volume":"9","author":"Lewkowicz","year":"2016","journal-title":"Mucosal Immunol."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/10\/1430\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:51:04Z","timestamp":1760035864000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/10\/1430"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,9]]},"references-count":75,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2025,10]]}},"alternative-id":["biom15101430"],"URL":"https:\/\/doi.org\/10.3390\/biom15101430","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,9]]}}}