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Immunol."],"abstract":"<jats:p>The IL-6 cytokine family signals through the common signal transduction molecule gp130 combined with a cytokine-specific receptor. Gp130 signaling on CD4 T cells is vital in controlling chronic infection of mice with lymphocytic choriomeningitis virus clone 13 (LCMV Cl13), but the precise role of individual members of the IL-6 cytokine family is not fully understood. Transcriptional analysis highlighted the importance of gp130 signaling in promoting key processes in CD4 T cells after LCMV Cl13 infection, particularly genes associated with T follicular helper (Tfh) cell differentiation and IL-21 production. Further, <jats:italic>Il27r<jats:sup>\u2212\/\u2212<\/jats:sup>Il6ra<jats:sup>\u2212\/\u2212<\/jats:sup><\/jats:italic> mice failed to generate antibody or CD8 T-cell immunity and to control LCMV Cl13. Transcriptomics and phenotypic analyses of <jats:italic>Il27r<jats:sup>\u2212\/\u2212<\/jats:sup>Il6ra<jats:sup>\u2212\/\u2212<\/jats:sup><\/jats:italic> Tfh cells revealed that IL-6R and IL-27R signaling was required to activate key pathways within CD4 T cells. IL-6 and IL-27 signaling has distinct and overlapping roles, with IL-6 regulating Tfh differentiation, IL-27 regulating CD4 T cell survival, and both redundantly promoting IL-21.<\/jats:p>","DOI":"10.3389\/fimmu.2023.1221562","type":"journal-article","created":{"date-parts":[[2023,7,31]],"date-time":"2023-07-31T16:11:30Z","timestamp":1690819890000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["IL-6 and IL-27 play both distinct and redundant roles in regulating CD4 T-cell responses during chronic viral infection"],"prefix":"10.3389","volume":"14","author":[{"given":"James A.","family":"Harker","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trever T.","family":"Greene","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Burton 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