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Several accessory proteins, such as UNC93B1, are required for transport and activation of nucleic acid sensing Toll-like receptors in endosomes. Here, we show that BAD-LAMP (LAMP5) controls TLR9 trafficking to LAMP1<jats:sup>+<\/jats:sup> late endosomes in human plasmacytoid dendritic cells (pDC), leading to NF-\u03baB activation and TNF production upon DNA detection. An inducible VAMP3<jats:sup>+\/<\/jats:sup>LAMP2<jats:sup>+\/<\/jats:sup>LAMP1<jats:sup>\u2212<\/jats:sup> endolysosome compartment exists in pDCs from which TLR9 activation triggers type I interferon expression. BAD-LAMP-silencing enhances TLR9 retention in this compartment and consequent downstream signalling events. Conversely, sustained BAD-LAMP expression in pDCs contributes to their lack of type I interferon production after exposure to a TGF-\u03b2-positive microenvironment or isolation from human breast tumours. Hence, BAD-LAMP limits interferon expression in pDCs indirectly, by promoting TLR9 sorting to late endosome compartments at steady state and in response to immunomodulatory cues.<\/jats:p>","DOI":"10.1038\/s41467-017-00695-1","type":"journal-article","created":{"date-parts":[[2017,10,9]],"date-time":"2017-10-09T10:54:45Z","timestamp":1507546485000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":72,"title":["BAD-LAMP controls TLR9 trafficking and signalling in human plasmacytoid dendritic cells"],"prefix":"10.1038","volume":"8","author":[{"given":"Alexis","family":"Combes","sequence":"first","affiliation":[]},{"given":"Voahirana","family":"Camosseto","sequence":"additional","affiliation":[]},{"given":"Prudence","family":"N\u2019Guessan","sequence":"additional","affiliation":[]},{"given":"Rafael J.","family":"Arg\u00fcello","sequence":"additional","affiliation":[]},{"given":"Julie","family":"Mussard","sequence":"additional","affiliation":[]},{"given":"Christophe","family":"Caux","sequence":"additional","affiliation":[]},{"given":"Nathalie","family":"Bendriss-Vermare","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0863-8255","authenticated-orcid":false,"given":"Philippe","family":"Pierre","sequence":"additional","affiliation":[]},{"given":"Evelina","family":"Gatti","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2017,10,13]]},"reference":[{"key":"695_CR1","doi-asserted-by":"publisher","first-page":"783","DOI":"10.1016\/j.cell.2006.02.015","volume":"124","author":"S Akira","year":"2006","unstructured":"Akira, S., Uematsu, S. & Takeuchi, O. 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