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Specificity and potency of these compounds are essential requirements for clinical trial applications. In patients with hepatitis B virus (HBV) infections, sustained loss of hepatitis B surface antigen (HBsAg) is a therapeutic goal, which may be achievable by the sequential activation of follicular helper T cells (Tfh) and antibody\u2010secreting B cells. We aimed to elucidate whether novel TLR7 agonist, GS\u2010986, could activate immune responses involved in HBV elimination.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To clarify the impact of GS\u2010986 on pDCs, we quantified the expression levels of surface markers and evaluated for Tfh induction in a culture model consisting of human pDCs with allogeneic na\u00efve CD4<jats:sup>+<\/jats:sup> T cells. In addition, we examined whether GS\u2010986 could enhance HBs antibody production capacity using PBMC from CHB patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>pDCs from CHB patients had lower OX40L expression and as well as impaired capacity for Tfh induction compared with those from healthy donors. However, GS\u2010986\u2013stimulated pDCs from CHB patients expressed OX40L and produced IL\u20106 and IL\u201012, resulting in the induction of IL\u201021\u2013producing Tfh cells (CXCR5<jats:sup>+<\/jats:sup>PD\u20101<jats:sup>+<\/jats:sup>CD4<jats:sup>+<\/jats:sup>) from na\u00efve CD4<jats:sup>+<\/jats:sup> T cells. The Tfh\u2010inducing capacity of GS\u2010986 was reduced in the presence of an anti\u2010OX40L blocking antibody. Furthermore, GS\u2010986 promoted HBsAg\u2010specific antibody production in PBMCs from CHB patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>GS\u2010986 is an adjuvant that stimulates pDCs to induce Tfh differentiation and antigen\u2010specific B\u2010cell production. This immune profile may be beneficial for therapeutic application as an immune modulator in CHB patients.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.15568","type":"journal-article","created":{"date-parts":[[2023,4,8]],"date-time":"2023-04-08T10:31:40Z","timestamp":1680949900000},"page":"1213-1224","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Toll\u2010like receptor 7 agonist, GS\u2010986, is an immune\u2010stimulant inducing follicular helper T cells and expanding HBs antigen\u2010specific B cells <i>in vitro<\/i>"],"prefix":"10.1111","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2923-5204","authenticated-orcid":false,"given":"Taizo","family":"Mori","sequence":"first","affiliation":[{"name":"Department of Liver Disease, The Research Center for Hepatitis and Immunology National Center for Global Health and Medicine  Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7860-6916","authenticated-orcid":false,"given":"Sachiyo","family":"Yoshio","sequence":"additional","affiliation":[{"name":"Department of Liver Disease, The Research Center for Hepatitis and Immunology National Center for Global Health and Medicine  Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiori","family":"Yoshikawa","sequence":"additional","affiliation":[{"name":"Department of Liver Disease, The Research Center for Hepatitis and Immunology National Center for Global Health and Medicine  Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuriko","family":"Tsustui","sequence":"additional","affiliation":[{"name":"Department of Liver Disease, The Research Center for Hepatitis and Immunology National Center for Global Health and Medicine  Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihiro","family":"Sakata","sequence":"additional","affiliation":[{"name":"Department of Liver Disease, The Research Center for Hepatitis and Immunology National Center for Global Health and Medicine  Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuichi","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological Surgery I Hokkaido University Graduate School of Medicine  Sapporo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuzuru","family":"Sakamoto","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological Surgery I Hokkaido University Graduate School of Medicine  Sapporo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hironari","family":"Kawai","sequence":"additional","affiliation":[{"name":"Department of Surgery The Jikei University School of Medicine  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yosuke","family":"Osawa","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology International University of Health and Welfare Hospital  Tochigi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taiji","family":"Yamazoe","sequence":"additional","affiliation":[{"name":"Department of Liver Disease, The Research Center for Hepatitis and Immunology National Center for Global Health and Medicine  Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiko","family":"Aoki","sequence":"additional","affiliation":[{"name":"Department of Liver Disease, The Research Center for Hepatitis and Immunology National Center for Global Health and Medicine  Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon P.","family":"Fletcher","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Inc.  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