Sca-1 expression defines different developmental stages of mouse PDC that show functional heterogeneity in the endosomal but not lysosomal TLR9 response

ABSTRACT: Plasmacytoid dendritic cells (PDC) play an important role in innate and adaptive immunity and were shown to be identical to previously described natural IFN-M-NM-1-producing cells (NIP). 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- PDC are mainly found in the bone marrow, appear first during development, show a higher proliferative activity and represent the more precursor phenotype. Sca-1+ PDC are mostly located in secondary lymphoid organs and show higher expression of MHC class II molecules. Sca-1- PDC give rise to a Sca-1+ subset upon activation or in response to tissue-specific factors. Interestingly, in contrast to Sca-1- PDC, Sca-1+ PDC are defective in type I IFN 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- PDC. This data provides evidence for the molecular basis of the observed functional heterogeneity, as the intracellular isoform of Opn couples TLR9 signaling to IFN-M-NM-1 expression. Taken together, our results indicate that Sca-1- PDC are an early developmental stage of PDC with distinct innate functions representing the true murine NIP. The dataset comprises eight samples divided into two sample groups consisting of Sca-1(-) and Sca-1(+) PDCs collected from in vitro culture of differentiated bone marrow precursor cells using mFlt3-L

ORGANISM(S): Mus musculus

SUBMITTER: Stefan Tomiuk 

PROVIDER: E-GEOD-42860 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress