{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T14:01:00Z","timestamp":1791036060234,"version":"4.1.0"},"reference-count":32,"publisher":"Rockefeller University Press","issue":"6","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2009,6,8]]},"abstract":"<jats:p>Prior studies have demonstrated that cholera toxin (CT) and other cAMP-inducing factors inhibit interleukin (IL)-12 production from monocytes and dendritic cells (DCs). We show that CT inhibits Th1 responses in vivo in mice infected with Toxoplasma gondii. This correlated with low serum IL-12 levels and a selective reduction in the numbers of CD8\u03b1+ conventional DCs (cDCs) in lymphoid organs. CT inhibited the function of interferon (IFN) regulatory factor (IRF) 8, a transcription factor known to positively regulate IL-12p35 and p40 gene expression, and the differentiation of CD8\u03b1+ and plasmacytoid DCs (pDCs). Fluorescence recovery after photobleaching analysis showed that exposure to CT, forskolin, or dibutyryl (db) cAMP blocked LPS and IFN-\u03b3\u2013induced IRF8 binding to chromatin. Moreover, CT and dbcAMP inhibited the binding of IRF8 to the IFN-stimulated response element (ISRE)\u2013like element in the mouse IL-12p40 promoter, likely by blocking the formation of ISRE-binding IRF1\u2013IRF8 heterocomplexes. Furthermore, CT inhibited the differentiation of pDCs from fms-like tyrosine kinase 3 ligand\u2013treated bone marrow cells in vitro. Therefore, because IRF8 is essential for IL-12 production and the differentiation of CD8\u03b1+ cDCs and pDCs, these data suggest that CT and other Gs-protein agonists can affect IL-12 production and DC differentiation via a common mechanism involving IRF8.<\/jats:p>","DOI":"10.1084\/jem.20080912","type":"journal-article","created":{"date-parts":[[2009,6,2]],"date-time":"2009-06-02T00:46:01Z","timestamp":1243903561000},"page":"1227-1235","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":48,"title":["Cholera toxin inhibits IL-12 production and CD8\u03b1+ dendritic cell differentiation by cAMP-mediated inhibition of IRF8 function"],"prefix":"10.1084","volume":"206","author":[{"given":"Andrea","family":"la Sala","sequence":"first","affiliation":[{"name":"Laboratory of Molecular and Cellular Immunology, Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele, 00163 Rome, Italy 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