The TLR7 agonist, imiquimod, increases IFN-beta production and reduces the severity of experimental autoimmune encephalomyelitis.
Experimental autoimmune encephalomyelitis (EAE) is a well-characterised model of autoimmune inflammatory demyelination. Toll-like receptors (TLRs) recognise microbial components and initiate innate immune responses. We report in this study that TLR7 stimulation by imiquimod, a synthetic analog of ssRNA, suppresses disease severity in a chronic EAE model. Disease suppression is associated with increased IFN-beta production in spleens of mice treated with imiquimod. In vitro experiments on pDCs, which express high levels of TLR7 and are potent producers of IFN-beta, suggest that an amplification loop involving TLR7 and IFNAR is required for the observed effects.
O'Brien
Kate
K
Division of Clinical Neurology, University of Nottingham, Nottingham, United Kingdom.
Fitzgerald
Denise
D
Rostami
Abdolmohamad
A
Gran
Bruno
B
D000276:Adjuvants, Immunologic / Q000494:pharmacology / Q000627:therapeutic use*; D000634:Aminoquinolines / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology; D005260:Female; D000077271:Imiquimod; D016899:Interferon-beta / Q000235:genetics / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000378:metabolism; D053633:Receptor, Interferon alpha-beta / Q000172:deficiency; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D013601:T-Lymphocytes / Q000187:drug effects / Q000502:physiology
D000276:Adjuvants, Immunologic; D000634:Aminoquinolines; D012333:RNA, Messenger; D053633:Receptor, Interferon alpha-beta; D016899:Interferon-beta; D000077271:Imiquimod