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Their adjuvant activity involves activation of cAMP\/protein kinase A (PKA) signaling and inflammasome\/IL-1\u03b2 pathways in antigen presenting cells (APC). To get a further understanding of the signal transduction and downstream pathways activated in APCs by this group of adjuvants we have, employing quantitative proteomic analytic tools, investigated human monocytes at various time points after treatment with CT. We report the activation of three main biological pathways among upregulated proteins, peaking at 16\u2009hours of CT treatment: cellular organization, metabolism, and immune response. Specifically, in the further analyzed immune response pathway we note a strong upregulation of thrombospondin 1 (THBS1) and integrin \u03b21 (ITGB1) in response to CT as well as to mmCT and dmLT, mediated via cAMP\/PKA and NFKB signaling. Importantly, inhibition<jats:italic>in vitro<\/jats:italic>of THSB1 and ITGB1 in monocytes or primary dendritic cells using siRNA abrogated the ability of the treated APCs to promote an adjuvant-stimulated Th17 cell response when co-cultured with peripheral blood lymphocytes indicating the involvement of these molecules in the adjuvant action on APCs by CT, mmCT and dmLT.<\/jats:p>","DOI":"10.1038\/s41598-019-38726-0","type":"journal-article","created":{"date-parts":[[2019,2,26]],"date-time":"2019-02-26T11:49:58Z","timestamp":1551181798000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Proteomic analysis of cholera toxin adjuvant-stimulated human monocytes identifies Thrombospondin-1 and Integrin-\u03b21 as strongly upregulated molecules involved in adjuvant activity"],"prefix":"10.1038","volume":"9","author":[{"given":"Manuela","family":"Terrinoni","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan","family":"Holmgren","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Lebens","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8799-7645","authenticated-orcid":false,"given":"Maximilian","family":"Larena","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2019,2,26]]},"reference":[{"key":"38726_CR1","first-page":"274","volume":"24","author":"N Lycke","year":"1988","unstructured":"Lycke, N. & Holmgren, J. 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