Stimulation of Innate Immune Cells by Light-Activated TLR7/8 Agonists

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• 作者：Keun Ah Ryu ; Lalisa Stutts ; Janine K. Tom ; Rock J. Mancini ; Aaron P. Esser-Kahn
• 刊名：Journal of the American Chemical Society
• 出版年：2014
• 出版时间：August 6, 2014
• 年：2014
• 卷：136
• 期：31
• 页码：10823-10825
• 全文大小：292K
• ISSN：1520-5126

文摘

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-魏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.