Toll-like receptor 7 agonists and skin.
Toll-like receptor (TLR) 7 is an intracellular TLR that is expressed on membranes of endosomes and recognizes nucleosides and nucleotides from intracellular pathogens. Synthetic agonists of TLR7 comprise guanine nucleoside analogues, stabilized immune modulatory RNA, as well as imidoazoquinoline-based compounds. Activation of pattern recognition receptors such as TLR with appropriate agonists induces a sophisticated defense machinery of the innate immune system. Targeting TLR pathways represents a cleverly devised and promising therapeutic strategy. At present, imiquimod is the most frequently used TLR7 ligand in clinical practice and has been approved for the treatment of external genital warts and (pre-) cancerous skin lesions such as actinic keratoses and superficial basal cell carcinoma. Upon topical application, this TLR7 agonist induces increased production of interferon-alpha, interleukin-12, tumor necrosis factor-alpha and a Th1 prone immune response. Imiquimod enforces the recruitment of myeloid and plasmacytoid dendritic cell subtypes and cytotoxic T cells, and increases the capacity of antigen-presenting cells to induce reactive T cells. Based on its multifaceted functions including proapoptotic, antifibrotic, antiangiogenic and antiaging effects, several reports about the efficacy of imiquimod as a treatment of various other skin diseases exist. This review summarizes the current knowledge about the immunological mechanisms induced by the TLR7 agonist imiquimod as well as established clinical therapies and putative applications of TLR7 agonists in the near future.
Novak
Natalija
N
Department of Dermatology and Allergy, University of Bonn, Bonn, Germany. Natalija.Novak@ukb.uni-bonn.de
Yu
Chun-Feng
CF
Bieber
Thomas
T
Allam
Jean-Pierre
JP
D000634:Aminoquinolines / Q000494:pharmacology* / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D000077271:Imiquimod; D008024:Ligands; D012871:Skin Diseases / Q000188:drug therapy*; D017193:Skin Diseases, Viral / Q000188:drug therapy / Q000473:pathology; D012878:Skin Neoplasms / Q000188:drug therapy / Q000473:pathology; D051199:Toll-Like Receptor 7 / Q000819:agonists*
D000634:Aminoquinolines; D000970:Antineoplastic Agents; D008024:Ligands; D051199:Toll-Like Receptor 7; D000077271:Imiquimod