Publication Date:
2013-08-07
Description:
Plasmacytoid dendritic cells (pDCs) play an important role in innate and adaptive immunity and were shown to be identical to previously described natural IFN-α-producing (NIP) cells. Here, we describe two functionally distinct pDC subpopulations that are characterized by the differential expression of stem cell antigen-1 (Sca-1; Ly-6A/E). Sca-1 − pDCs are mainly found in the bone marrow, appear first during development, show a higher proliferative activity and represent the more precursor phenotype. Sca-1 + pDCs are mostly located in secondary lymphoid organs and represent a later developmental stage. Sca-1 − pDCs give rise to a Sca-1 + subset upon activation or in response to endogenous type I IFN. Interestingly, in contrast to Sca-1 − pDCs, Sca-1 + pDCs are defective in IFN-α production upon endosomal TLR9 stimulation, whereas lysosomal signaling via TLR9 is functional in both subsets. Gene expression analysis revealed that osteopontin (Opn) is strongly upregulated in Sca-1 − pDCs. These data provide evidence for the molecular basis of the observed functional heterogeneity, as the intracellular isoform of Opn couples TLR9 signaling to IFN-α expression. Taken together, our results indicate that Sca-1 − pDCs are an early developmental stage of pDCs with distinct innate functions representing the true murine NIP cell.
Print ISSN:
0014-2980
Electronic ISSN:
1521-4141
Topics:
Medicine
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