title: 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-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.
authors.affiliation: Department of Chemistry, University of California , Irvine, California 92697, United States.
authors.forename: Keun Ah
authors.initials: KA
authors.lastname: Ryu
authors.forename: Lalisa
authors.initials: L
authors.lastname: Stutts
authors.forename: Janine K
authors.initials: JK
authors.lastname: Tom
authors.forename: Rock J
authors.initials: RJ
authors.lastname: Mancini
authors.forename: Aaron P
authors.initials: AP
authors.lastname: Esser-Kahn
mesh_terms: D000634:Aminoquinolines / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D002460:Cell Line; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000528:radiation effects; D000077271:Imiquimod; D007113:Immunity, Innate / Q000187:drug effects* / Q000528:radiation effects*; D008027:Light; D051379:Mice; D008958:Models, Molecular; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D051199:Toll-Like Receptor 7 / Q000819:agonists* / Q000378:metabolism; D051200:Toll-Like Receptor 8 / Q000819:agonists* / Q000737:chemistry / Q000378:metabolism
chemical_list: D000634:Aminoquinolines; D051199:Toll-Like Receptor 7; D051200:Toll-Like Receptor 8; D000077271:Imiquimod