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These findings revealed that IL\u201013 and IL\u20104 differentially regulated antibody development. To understand this further, when STAT6<jats:sup>\u2212\/\u2212<\/jats:sup> mice were given a vaccine co\u2010expressing IL\u201013R\u03b12 that temporarily sequestered IL\u201013, significantly reduced IgG2a expression, was detected. These findings for the first time demonstrated that IL\u201013 regulated IgG2a differentiation utilising an alternative IL\u201013R signalling pathway independent of STAT6 (IL\u201013R\u03b12 pathway). This was further corroborated by the (i) elevated IL\u201013R\u03b12 expression detected on STAT6<jats:sup>\u2212\/\u2212<\/jats:sup> lung MHCII<jats:sup>+<\/jats:sup> CD11c<jats:sup>+<\/jats:sup> cells 24 h post IL\u201013 inhibitor vaccination and ii) significant up\u2010regulation of IL\u201013R\u03b12 expression on spleen and lung derived MHCII<jats:sup>+<\/jats:sup>CD11c<jats:sup>+<\/jats:sup> following inhibition of STAT6 signalling in vitro, or vaccination with IL\u20104R\/STAT6 antagonist in vivo. When T follicular helper (Tfh) cells which regulate antibody differentiation were assessed post vaccination, although no difference in IL\u20104 expression was observed, greatly reduced IFN\u2010\u03b3 expression was detected in IL\u201013<jats:sup>\u2212\/\u2212<\/jats:sup> and STAT6<jats:sup>\u2212\/\u2212<\/jats:sup> mice compared to wild\u2010type. These findings support the notion that the balance of IL\u201013 level at the vaccination site can differentially regulate T and B\u2010cell immune outcomes.<\/jats:p>","DOI":"10.1002\/eji.201747463","type":"journal-article","created":{"date-parts":[[2018,3,23]],"date-time":"2018-03-23T11:39:07Z","timestamp":1521805147000},"page":"1153-1163","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Unexpected involvement of IL\u201013 signalling via a STAT6 independent mechanism during murine IgG2a development following viral vaccination"],"prefix":"10.1002","volume":"48","author":[{"given":"Megat Abd","family":"Hamid","sequence":"first","affiliation":[{"name":"Molecular Mucosal Vaccine Immunology Group Department of Immunology and infectious Disease The John Curtin School of Medical Research The Australian National University  Canberra Australia"},{"name":"MRC Human Immunology Unit Weatherall Institute of Molecular 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