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Recently, CT was reported to induce T helper type 17\u2010skewing dendritic cells and activate interleukin\u201017A (IL\u201017A) production in CD4<jats:sup>+<\/jats:sup> T cells through a cAMP\u2010dependent pathway. However, the underlying mechanism by which cAMP regulates IL\u201017A production in T cells is not completely defined. In this study, we took advantage of a small molecule protein kinase A (PKA) inhibitor (H89) and different cAMP analogues: a PKA\u2010specific activator (N6\u2010benzoyl\u2010adenosine\u2010cAMP), an exchange protein activated by cAMP\u2010specific activator (Rp\u20108\u2010chlorophenylthio\u20102\u2032\u2010<jats:italic>O<\/jats:italic>\u2010methyl cAMP), and a PKA inhibitor (Rp\u20108\u2010bromo\u2010cAMP), to elucidate the signalling cascade of cAMP in IL\u201017A regulation in T cells. We found that CT induced IL\u201017A production and IL\u201017A promoter activity in activated CD4<jats:sup>+<\/jats:sup> T cells through a cAMP\/PKA pathway. Moreover, this regulation was via cAMP\u2010response element binding protein (CREB) \u2010mediated transcriptional activation by using the transfection of an IL\u201017A promoter\u2013luciferase reporter construct and CREB small interfering RNA in Jurkat cells. Also, we showed that CREB bound to the CRE motif located at \u2212183 of the IL\u201017A promoter <jats:italic>in\u00a0vitro<\/jats:italic>. Most interestingly, not only in CD4<jats:sup>+<\/jats:sup> T cells, CT also enhanced cAMP\/PKA\u2010dependent IL\u201017A production and CREB phosphorylation in CD8<jats:sup>+<\/jats:sup> T cells. In conclusion, our data suggest that CT induces an IL\u201017A\u2010dominated immune microenvironment through the cAMP\/PKA\/CREB signalling pathway. Our study also highlights the potentials of CT and cAMP in modulating T helper type 17 responses <jats:italic>in\u00a0vivo<\/jats:italic>.<\/jats:p>","DOI":"10.1111\/imm.12900","type":"journal-article","created":{"date-parts":[[2018,1,29]],"date-time":"2018-01-29T19:56:42Z","timestamp":1517255802000},"page":"500-509","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Cholera toxin enhances interleukin\u201017A production in both CD4<sup>+<\/sup> and CD8<sup>+<\/sup> cells via a cAMP\/protein kinase A\u2010mediated interleukin\u201017A promoter activation"],"prefix":"10.1111","volume":"154","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8972-7174","authenticated-orcid":false,"given":"Hsing\u2010Chuan","family":"Tsai","sequence":"first","affiliation":[{"name":"Center for Comparative Respiratory Biology and Medicine University of California Davis CA USA"},{"name":"Department of Neurology and Neurological Sciences 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