Expression of Sca-1 (Ly-6A/E) defines functionally different developmental stages of plasmacytoid dendritic cells (PDC) (84.9)

Abstract

Stem cell antigen-1 (Sca-1), a phosphatidylinositol-linked membrane protein is one of the most prominent stem cell markers. Functionally, Sca-1 is involved in cross-talk between lymphocyte precursors and stromal cells and plays an important role in the thymic development of T-cells and TcR-dependent activation. Here we show that expression of Sca-1 on PDC defines functionally different developmental stages of PDC in mice. The proportion of the Sca-1+ PDC showed an organ specific variation ranging from 10-20% in BM to >80% in LN. Sca-1- PDC appeared earlier in the development and give rise to Sca-1+ PDC without the need for activation. In addition to the naturally occurring up-regulation, Sca-1 expression could be further induced by TLR7 and TLR9 mediated activation. Interestingly, when exposed to CpG-oligonucleotides (TLR9), Sca-1- PDC produced significantly higher amounts of IFN-alpha. This was further confirmed by two observations: (1) after stimulation with TLR9-ligands purified PDC from BM (mainly Sca-1-) produced up to 100-fold higher amounts of IFN-alpha when compared to PDC from LN (predominantly Sca-1+), (2) Sca-1- PDC expressed significantly higher amount of genes involved in TLR mediated IFN-alpha induction, including MyD88, IRF3, IRF5, IFNAR1 and IFNAR2. Taking together, our results identify Sca-1 as a developmental marker of PDC, which defines two functionally heterogeneous subsets of PDC.