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The PC dictates that ES-62 exhibits protection in murine models of inflammatory disease and hence a library of drug-like PC-based small molecule analogues (SMAs) was synthesised. Four sulfone-containing SMAs termed 11a, 11e, 11i and 12b were found to reduce mouse bone marrow-derived dendritic cell (DC) pathogen-associated molecular pattern (PAMP)-induced pro-inflammatory cytokine production, inhibit NF-\u03baB p65 activation, and suppress LPS-induced up-regulation of CD40 and CD86. Active SMAs also resulted in a DC phenotype that exhibited reduced capacity to prime antigen (Ag)-specific IFN-\u03b3 production during co-culture with na\u00efve transgenic TCR DO.11.10 T cells <jats:italic>in vitro<\/jats:italic> and reduced their ability, following adoptive transfer, to prime the expansion of Ag-specific T lymphocytes, specifically T<jats:sub>H<\/jats:sub>17 cells, <jats:italic>in vivo<\/jats:italic>. Consistent with this, mice receiving DCs treated with SMAs exhibited significantly reduced severity of collagen-induced arthritis and this was accompanied by a significant reduction in IL-17<jats:sup>+<\/jats:sup> cells in the draining lymph nodes. Collectively, these studies indicate that drug-like compounds that target DCs can be designed from parasitic worm products and demonstrate the potential for ES-62 SMA-based DC therapy in inflammatory disease.<\/jats:p>","DOI":"10.1038\/s41598-017-01651-1","type":"journal-article","created":{"date-parts":[[2017,5,4]],"date-time":"2017-05-04T14:32:32Z","timestamp":1493908352000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Dendritic cells provide a therapeutic target for synthetic small molecule analogues of the parasitic worm product, ES-62"],"prefix":"10.1038","volume":"7","author":[{"given":"Felicity E.","family":"Lumb","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Doonan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kara S.","family":"Bell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel A.","family":"Pineda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marlene","family":"Corbet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin J.","family":"Suckling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5740-3028","authenticated-orcid":false,"given":"Margaret M.","family":"Harnett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Harnett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,5,10]]},"reference":[{"key":"1651_CR1","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1038\/ni.1863","volume":"11","author":"T Kawai","year":"2010","unstructured":"Kawai, T. & Akira, S. 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