{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:40:29Z","timestamp":1790836829232,"version":"4.1.0"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,8,26]],"date-time":"2021-08-26T00:00:00Z","timestamp":1629936000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Identifying signaling pathways that induce B cell response can aid functional cure strategies for chronic hepatitis B infection (CHB). TLR8 activation with ssRNA was shown to enhance follicular helper T cell (T\n                    <jats:sub>FH<\/jats:sub>\n                    ) function leading to improved B cell responses\n                    <jats:italic>in vitro<\/jats:italic>\n                    . We investigated whether this mechanism can rescue an exhausted immune response in CHB infection. Effect of TLR8 agonism on supporting cytokines and T\n                    <jats:sub>FH<\/jats:sub>\n                    and B cells were evaluated using\n                    <jats:italic>ex vivo<\/jats:italic>\n                    and\n                    <jats:italic>in vitro<\/jats:italic>\n                    assays. The ability of an oral TLR8 agonist to promote T\n                    <jats:sub>FH<\/jats:sub>\n                    and B cell response was tested in samples from phase 1b clinical trial. TLR8 agonism induced T\n                    <jats:sub>FH<\/jats:sub>\n                    polarizing cytokine IL-12 in monocytes. Treatment of peripheral blood mononuclear cells (PBMCs) from CHB patients with TLR8 agonists induced cytokine IL-21 by T\n                    <jats:sub>FH<\/jats:sub>\n                    cells with enhanced IL-21\n                    <jats:sup>+<\/jats:sup>\n                    BCL-6\n                    <jats:sup>+<\/jats:sup>\n                    and ICOS\n                    <jats:sup>+<\/jats:sup>\n                    BCL-6\n                    <jats:sup>+<\/jats:sup>\n                    co-expression. Mechanistically, incubation of isolated na\u00efve CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells with TLR8 triggered monocytes resulted in their differentiation into IL-21\n                    <jats:sup>+<\/jats:sup>\n                    ICOS\n                    <jats:sup>+<\/jats:sup>\n                    BCL-6\n                    <jats:sup>+<\/jats:sup>\n                    T\n                    <jats:sub>FH<\/jats:sub>\n                    in an IL-12 dependent manner. Furthermore, co-culture of these IL-21 producing T\n                    <jats:sub>FH<\/jats:sub>\n                    with autologous na\u00efve B cells led to enhanced memory (CD19\n                    <jats:sup>+<\/jats:sup>\n                    CD27\n                    <jats:sup>+<\/jats:sup>\n                    ) and plasma B cell generation (CD19\n                    <jats:sup>+<\/jats:sup>\n                    CD27\n                    <jats:sup>++<\/jats:sup>\n                    CD38\n                    <jats:sup>+<\/jats:sup>\n                    ) and IgG production. Importantly, in T\n                    <jats:sub>FH<\/jats:sub>\n                    from CHB patients treated with an oral TLR8 agonist, HBsAg-specific BCL-6, ICOS, IL-21 and CD40L expression and rescue of defective activation induced marker (AIM) response along with partial restoration of HBsAg-specific B cell ELISPOT response was evident. TLR8 agonism can thus enhance HBV-specific B cell responses in CHB patients by improving monocyte-mediated T\n                    <jats:sub>FH<\/jats:sub>\n                    function and may play a role in achieving HBV functional cure.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2021.735913","type":"journal-article","created":{"date-parts":[[2021,8,27]],"date-time":"2021-08-27T16:52:46Z","timestamp":1630083166000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":31,"title":["Follicular Helper T (TFH) Cell Targeting by TLR8 Signaling For Improving HBsAg-Specific B Cell Response In Chronic Hepatitis B Patients"],"prefix":"10.3389","volume":"12","author":[{"given":"Natarajan","family":"Ayithan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lydia","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanna K.","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey J.","family":"Wallin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon P.","family":"Fletcher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shyam","family":"Kottilil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhawna","family":"Poonia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,8,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2016.196","article-title":"HBV in 2016: Global and Immunotherapeutic Insights Into Hepatitis B","volume":"14","author":"Maini","year":"2017","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/S2468-1253(19)30119-0","article-title":"A Global Scientific Strategy to Cure Hepatitis B","volume":"4","author":"Revill","year":"2019","journal-title":"Lancet Gastroenterol 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