{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T17:07:30Z","timestamp":1791220050349,"version":"4.1.0"},"reference-count":54,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2013,8,27]],"date-time":"2013-08-27T00:00:00Z","timestamp":1377561600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2013,11]]},"abstract":"Plasmacytoid dendritic cells (pDC<\/jats:styled-content>s) play an important role in innate and adaptive immunity and were shown to be identical to previously described natural interferon (IFN<\/jats:styled-content>)\u2010\u03b1\u2010producing cells. Here, we describe two functionally distinct pDC<\/jats:styled-content> subpopulations that are characterized by the differential expression of stem cell antigen\u20101 (S<\/jats:styled-content>ca\u20101; L<\/jats:styled-content>y\u20106A\/E<\/jats:styled-content>). Sca\u20101\u2212<\/jats:sup> pDC<\/jats:styled-content>s are mainly found in the BM<\/jats:styled-content>, appear first during development, show a higher proliferative activity, and represent the more precursor phenotype. Sca\u20101+<\/jats:sup> pDC<\/jats:styled-content>s are mostly located in secondary lymphoid organs and represent a later developmental stage. Sca\u20101\u2212<\/jats:sup> pDC<\/jats:styled-content>s give rise to an S<\/jats:styled-content>ca\u20101+<\/jats:sup> subset upon activation or in response to endogenous type I IFN<\/jats:styled-content>. Interestingly, in contrast to S<\/jats:styled-content>ca\u20101\u2212<\/jats:sup> pDC<\/jats:styled-content>s, S<\/jats:styled-content>ca\u20101+<\/jats:sup> pDC<\/jats:styled-content>s are defective in IFN<\/jats:styled-content>\u2010\u03b1 production upon endosomal TLR<\/jats:styled-content>9 stimulation, whereas lysosomal signaling via TLR<\/jats:styled-content>9 is functional in both subsets. Gene expression analysis revealed that osteopontin is strongly upregulated in S<\/jats:styled-content>ca\u20101\u2212<\/jats:sup> pDC<\/jats:styled-content>s. These data provide evidence for the molecular basis of the observed functional heterogeneity, as the intracellular isoform of osteopontin couples TLR<\/jats:styled-content>9 signaling to IFN<\/jats:styled-content>\u2010\u03b1 expression. Taken together, our results indicate that S<\/jats:styled-content>ca\u20101\u2212<\/jats:sup> pDC<\/jats:styled-content>s are an early developmental stage of pDC<\/jats:styled-content>s with distinct innate functions representing the true murine natural IFN<\/jats:styled-content>\u2010\u03b1\u2010producing cells.<\/jats:p>","DOI":"10.1002\/eji.201343498","type":"journal-article","created":{"date-parts":[[2013,8,6]],"date-time":"2013-08-06T11:18:05Z","timestamp":1375787885000},"page":"2993-3005","source":"Crossref","is-referenced-by-count":26,"title":["S<\/scp>ca\u20101 expression defines developmental stages of mouse pDC<\/scp>s that show functional heterogeneity in the endosomal but not lysosomal TLR<\/scp>9 response"],"prefix":"10.1002","volume":"43","author":[{"given":"Marina","family":"Niederquell","sequence":"first","affiliation":[{"name":"Miltenyi Biotec GmbH Bergisch Gladbach Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie","family":"Kurig","sequence":"additional","affiliation":[{"name":"Miltenyi Biotec GmbH Bergisch Gladbach Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens A. 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