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Stimulation of innate immune cells by light-activated TLR7/8 agonists.


ABSTRACT: 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-?B 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.

SUBMITTER: Ryu KA 

PROVIDER: S-EPMC4132957 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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Stimulation of innate immune cells by light-activated TLR7/8 agonists.

Ryu Keun Ah KA   Stutts Lalisa L   Tom Janine K JK   Mancini Rock J RJ   Esser-Kahn Aaron P AP  

Journal of the American Chemical Society 20140728 31


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 suppress  ...[more]

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