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IL\u201023 signal, acting as a switch, turns on pathogenicity of CD4<jats:sup>+<\/jats:sup> T cells, and becomes dispensable once autoreactivity is established. <jats:italic>Il23a<jats:sup>\u2212\/\u2212<\/jats:sup><\/jats:italic> mice failed to mount an efficient Th17 response to immunization, and were protected from myocarditis. However, remarkably, transient IL\u201023 stimulation ex vivo fully restored pathogenicity in otherwise nonpathogenic CD4<jats:sup>+<\/jats:sup> T cells raised from <jats:italic>Il23a<jats:sup>\u2212\/\u2212<\/jats:sup><\/jats:italic> donors. Thus, IL\u201023 may no longer be necessary to uphold inflammation in established autoimmune diseases. In addition, we demonstrated that IL\u201023\u2010induced GM\u2010CSF mediates the pathogenicity of CD4<jats:sup>+<\/jats:sup> T cells in EAM. The neutralization of GM\u2010CSF abrogated cardiac inflammation. However, sustained IL\u201023 signaling is required to maintain IL\u201017A production in CD4<jats:sup>+<\/jats:sup> T cells. Despite inducing inflammation in <jats:italic>Il23a<jats:sup>\u2212\/\u2212<\/jats:sup><\/jats:italic> recipients comparable to wild\u2010type (WT), autoreactive CD4<jats:sup>+<\/jats:sup> T cells downregulated IL\u201017A production without persistent IL\u201023 signaling. This divergence on the controls of GM\u2010CSF\u2010dependent pathogenicity on one side and IL\u201017A production on the other side may contribute to the discrepant efficacies of anti\u2010IL\u201023 therapy in different autoimmune diseases.<\/jats:p>","DOI":"10.1002\/eji.201545924","type":"journal-article","created":{"date-parts":[[2015,12,14]],"date-time":"2015-12-14T13:37:14Z","timestamp":1450100234000},"page":"582-592","source":"Crossref","is-referenced-by-count":39,"title":["Pathogenic IL\u201023 signaling is required to initiate GM\u2010CSF\u2010driven autoimmune myocarditis in mice"],"prefix":"10.1002","volume":"46","author":[{"given":"Lei","family":"Wu","sequence":"first","affiliation":[{"name":"W. 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