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PDA\u2010001 (cenplacel\u2010L), an intravenous formulation of PDAC cells, is in clinical development for the treatment of autoimmune and inflammatory diseases. To elucidate the mechanisms underlying the immunoregulatory properties of PDAC cells, we investigated their effects on immune cell populations, including T cells and dendritic cells (DC) <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>. PDAC cells suppressed T\u2010cell proliferation in an OT\u2010II T\u2010cell adoptive transfer model, reduced the severity of myelin oligodendrocyte glycoprotein peptide\u2010induced experimental autoimmune encephalomyelitis and ameliorated inflammation in a delayed type hypersensitivity response model. <jats:italic>In vitro<\/jats:italic>, PDAC cells suppressed T\u2010cell proliferation and inhibited Th1 and Th17 differentiation. Analysis of tissues derived from PDAC cell\u2010treated animals revealed diminished CD86 expression on splenic DC, suggesting that they can also modulate DC populations. Furthermore, PDAC cells modulate the differentiation and maturation of mouse bone marrow\u2010derived DC. Similarly, human DC differentiated from CD14<jats:sup>+<\/jats:sup> monocytes in the presence of PDAC cells acquired a tolerogenic phenotype. These tolerogenic DC failed to induce allogeneic T\u2010cell proliferation and differentiation toward Th1, but skewed T\u2010cell differentiation toward Th2. Inhibition of cyclo\u2010oxygenase\u20102 activity resulted in a significant, but not complete, abrogation of PDAC cells\u2019 effects on DC phenotype and function, implying a role for prostaglandin E2 in PDAC\u2010mediated immunomodulation. This study identifies modulation of DC differentiation toward immune tolerance as a key mechanism underlying the immunomodulatory activities of PDAC cells.<\/jats:p>","DOI":"10.1038\/cti.2014.5","type":"journal-article","created":{"date-parts":[[2014,5,2]],"date-time":"2014-05-02T07:41:03Z","timestamp":1399016463000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Human placenta\u2010derived adherent cells induce tolerogenic immune responses"],"prefix":"10.1002","volume":"3","author":[{"given":"Wei","family":"Liu","sequence":"first","affiliation":[{"name":"Celgene Cellular Therapeutics  Warren NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Morschauser","sequence":"additional","affiliation":[{"name":"Celgene Cellular Therapeutics  Warren NJ 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