Stimulation of innate immune cells by light-activated TLR7/8 agonists.
- Author(s): Ryu, Keun Ah
- Stutts, Lalisa
- Tom, Janine K
- Mancini, Rock J
- Esser-Kahn, Aaron P
- et al.
Published Web Locationhttps://doi.org/10.1021/ja412314j
The innate immune response is controlled, in part, by the synergistic interaction of multiple Toll-like receptors (TLRs). This multi-receptor cooperation is responsible for the potent activity of many vaccines, but few tools have been developed to understand the spatio-temporal elements of TLR synergies. In this Communication, we present photo-controlled agonists of TLR7/8. By strategically protecting the active agonist moiety based on an agonist-bound crystal structure, TLR activity is suppressed and then regained upon exposure to light. We confirmed NF-κB production upon light exposure in a model macrophage cell line. Primary cell activity was confirmed by examining cytokine and cell surface marker production in bone-marrow-derived dendritic cells. Finally, we used light to activate dendritic cell sub-populations within a larger population.