A novel β-glucan-oligonucleotide complex selectively delivers siRNA to APCs via Dectin-1.

Delivering therapeutic nucleic acids to targeted cells and organs has been a challenge for decades. A novel technology to deliver oligonucleotide therapeutics to immune cells is here described. In this approach, a macromolecular complex of oligonucleotides and the β-1,3-glucan schizophyllan (SPG) is selectively delivered to cells expressing a lectin receptor, Dectin-1, via SPG-Dectin-1 interaction.

In vivo and in vitro analyses of α-galactosylceramide uptake by conventional dendritic cell subsets using its fluorescence-labeled derivative.

Conventional dendritic cells (cDCs) present α-galactosylceramide (αGC) to invariant natural killer T (iNKT) cells through CD1d. Among cDC subsets, CD8(+) DCs efficiently induce IFN-γ production in iNKT cells. Using fluorescence-labeled αGC, we showed that CD8(+) DCs incorporated larger amounts of αGC and kept it intact longer than CD8(-) DCs.

Sulfatide inhibits α-galactosylceramide presentation by dendritic cells.

Sulfatide-reactive type II NKT cells, the so-called non-invariant NKT (non-iNKT) cells, have been shown to counteract invariant NKT (iNKT) cell activity. However, the effects of sulfatide on activation of iNKT cells by α-galactocylceramide (αGC) in the context of CD1d have not been studied in detail. Therefore, we studied the blocking effect of sulfatide on αGC-induced iNKT cell activation by dendritic cells (DCs).

Invariant NKT cell anergy is induced by a strong TCR-mediated signal plus co-stimulation.

Vα14 TCR expressing invariant NK T (iNKT) cells recognize α-galactosylceramide (αGC)/CD1d complex and produce large amounts of various cytokines before the onset of the adaptive immunity. After stimulation with a high dose (2-5 μg) of αGC in vivo, iNKT cells in the spleen and liver become anergic in terms of the proliferation and cytokine production to subsequent stimulation. In this study, we monitor how iNKT anergy is induced.