{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T09:32:25Z","timestamp":1791279145159,"version":"4.1.0"},"reference-count":50,"publisher":"American Society for Microbiology","issue":"16","license":[{"start":{"date-parts":[[2014,8,15]],"date-time":"2014-08-15T00:00:00Z","timestamp":1408060800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2014,8,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            T follicular helper (Tfh) cells are specialized providers of cognate B cell help, which is important in promoting the induction of high-affinity antibody production in germinal centers (GCs). Interleukin-6 (IL-6) and IL-21 have been known to play important roles in Tfh cell differentiation. Here, we demonstrate that IL-7 plays a pivotal role in Tfh generation and GC formation\n            <jats:italic>in vivo<\/jats:italic>\n            , as treatment with anti-IL-7 neutralizing antibody markedly impaired the development of Tfh cells and IgG responses. Moreover, codelivery of mouse Fc-fused IL-7 (IL-7-mFc) with a vaccine enhanced the generation of GC B cells as well as Tfh cells but not other lineages of T helper cells, including Th1, Th2, and Th17 cells. Interestingly, a 6-fold-lower dose of an influenza virus vaccine codelivered with Fc-fused IL-7 induced higher antigen-specific and cross-reactive IgG titers than the vaccine alone in both mice and monkeys and led to markedly enhanced protection against heterologous influenza virus challenge in mice. Enhanced generation of Tfh cells by IL-7-mFc treatment was not significantly affected by the neutralization of IL-6 and IL-21, indicating an independent role of IL-7 on Tfh differentiation. Thus, IL-7 holds promise as a critical cytokine for selectively inducing Tfh cell generation and enhancing protective IgG responses.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            Here, we demonstrate for the first time that codelivery of Fc-fused IL-7 significantly increased influenza virus vaccine-induced antibody responses, accompanied by robust expansion of Tfh cells and GC B cells as well as enhanced GC formation. Furthermore, IL-7-mFc induced earlier and cross-reactive IgG responses, leading to striking protection against heterologous influenza virus challenge. These results suggest that Fc-fused IL-7 could be used for inducing strong and cross-protective humoral immunity against highly mutable viruses, such as HIV and hepatitis C virus, as well as influenza viruses.\n          <\/jats:p>","DOI":"10.1128\/jvi.00534-14","type":"journal-article","created":{"date-parts":[[2014,6,5]],"date-time":"2014-06-05T01:56:57Z","timestamp":1401933417000},"page":"8998-9009","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":73,"title":["Crucial Roles of Interleukin-7 in the Development of T Follicular Helper Cells and in the Induction of Humoral Immunity"],"prefix":"10.1128","volume":"88","author":[{"given":"Yong Bok","family":"Seo","sequence":"first","affiliation":[{"name":"Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Gyungbuk, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Se Jin","family":"Im","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Gyungbuk, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Namkoong","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Gyungbuk, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sae Won","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Gyungbuk, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young Woo","family":"Choi","sequence":"additional","affiliation":[{"name":"Intergrative Biosciences and Biotechnology, Pohang University of Science and Technology (POSTECH), Pohang, Gyungbuk, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moon Cheol","family":"Kang","sequence":"additional","affiliation":[{"name":"Intergrative Biosciences and Biotechnology, Pohang University of Science and Technology (POSTECH), Pohang, Gyungbuk, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hye Seong","family":"Lim","sequence":"additional","affiliation":[{"name":"Research Institute, Genexine Co. Ltd., Seongnam, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun Tak","family":"Jin","sequence":"additional","affiliation":[{"name":"Research Institute, Genexine Co. Ltd., Seongnam, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Se Hwan","family":"Yang","sequence":"additional","affiliation":[{"name":"Research Institute, Genexine Co. Ltd., Seongnam, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mi La","family":"Cho","sequence":"additional","affiliation":[{"name":"Rheumatism Research Center, Catholic Institutes of Medical Science, Seoul, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"You-Me","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Gyungbuk, Republic of Korea"},{"name":"Intergrative Biosciences and Biotechnology, Pohang University of Science and Technology (POSTECH), Pohang, Gyungbuk, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung-Woo","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Gyungbuk, Republic of Korea"},{"name":"Intergrative Biosciences and Biotechnology, Pohang University of Science and Technology (POSTECH), Pohang, Gyungbuk, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young Ki","family":"Choi","sequence":"additional","affiliation":[{"name":"College of Medicine and Medical Research Institute, Chungbuk National University, Cheongju, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles D.","family":"Surh","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Gyungbuk, Republic of Korea"},{"name":"Intergrative Biosciences and Biotechnology, Pohang University of Science and Technology (POSTECH), Pohang, Gyungbuk, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young Chul","family":"Sung","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Gyungbuk, Republic of Korea"},{"name":"Intergrative Biosciences and Biotechnology, Pohang University of Science and Technology (POSTECH), Pohang, Gyungbuk, Republic of Korea"},{"name":"Research Institute, Genexine Co. Ltd., Seongnam, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.86.1.302"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1136736"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-031210-101400"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.10.036"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1175870"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20120994"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1208421"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2008.05.009"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2008.06.001"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20100064"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0017739"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200939271"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0024574"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2009.09.018"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0264-410X(97)88856-1"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.02045-09"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02403-09"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2011.03.023"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.5.2731"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.19.10348"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.9.5827"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3002400"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-020711-075032"},{"key":"e_1_3_2_25_2","first-page":"2254","article-title":"Relationship of germinal centers in lymphoid tissue to immunologic memory. VI","volume":"131","author":"Coico RF","year":"1983","unstructured":"CoicoRFBhogalBSThorbeckeGJ. 1983. Relationship of germinal centers in lymphoid tissue to immunologic memory. VI. Transfer of B cell memory with lymph node cells fractionated according to their receptors for peanut agglutinin. J. Immunol. 131:2254\u20132257.","journal-title":"Transfer of B cell memory with lymph node cells fractionated according to their receptors for peanut agglutinin. J. Immunol."},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201141748"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-032712-095916"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20071681"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2011.07.025"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI23134"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2010.10.007"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.7.4927"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.4.2340"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1203032"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2011.11.012"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1176676"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0803666"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20090153"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1204327109"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2011.07.015"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1100853"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2010.07.015"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1704"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri2580"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V92.1.93.413a03_93_100"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-08-176321"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1201757"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2009.07.005"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(03)00208-5"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1002497"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2009.04.016"}],"container-title":["Journal of Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.00534-14","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.00534-14","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,5]],"date-time":"2022-03-05T15:40:40Z","timestamp":1646494840000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/JVI.00534-14"}},"subtitle":[],"editor":[{"given":"D. S.","family":"Lyles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2014,8,15]]},"references-count":50,"journal-issue":{"issue":"16","published-print":{"date-parts":[[2014,8,15]]}},"alternative-id":["10.1128\/JVI.00534-14"],"URL":"https:\/\/doi.org\/10.1128\/jvi.00534-14","relation":{},"ISSN":["0022-538X","1098-5514"],"issn-type":[{"value":"0022-538X","type":"print"},{"value":"1098-5514","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,8,15]]},"assertion":[{"value":"2014-02-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-05-23","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-07-22","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}