Toll-like receptors： potential targets for lupus treatment  

作　　者：Yan-wei WU Wei TANG Jian-ping ZUO 

机构地区：[1]Laboratory of Immunopharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China

出　　处：《Acta Pharmacologica Sinica》2015年第12期1395-1407,共13页中国药理学报（英文版）

基　　金：This work was supported by grants from the National Natu- ral Science Foundation of China （No 81273524, 81273525, and 81322049） and the National Key Basic Research Program （973 Program, 2014CB541906）.

摘　　要：Systemic lupus erythematosus （SLE） is a complex autoimmune disease characterized by the loss of tolerance to self-nuclear antigens. Accumulating evidence shows that Toll-like receptors （TLRs）, previously proven to be critical for host defense, are implicated in the pathogenesis of autoimmune diseases by recognition of self-molecules. Genome-wide association studies, experimental mouse models and clinical sample studies have provided evidence for the involvement of TLRs, including TLR2/4, TLR5, TLR3 and TLR7/8/9, in SLE pathogenesis. A number of downstream proteins in the TLR signaling cascade （such as MyD88, IRAKs and IFN-a） are identified as potential therapeutic targets for SLE treatment. Numerous antagonists targeting TLR signaling, including oligonucleotides, small molecular inhibitors and antibodies, are currently under preclinical studies or clinical trials for SLE treatment. Moreover, the emerging new manipulation of TLR signaling by microRNA （miRNA） regulation shows promise for the future treatment of SLE.Systemic lupus erythematosus （SLE） is a complex autoimmune disease characterized by the loss of tolerance to self-nuclear antigens. Accumulating evidence shows that Toll-like receptors （TLRs）, previously proven to be critical for host defense, are implicated in the pathogenesis of autoimmune diseases by recognition of self-molecules. Genome-wide association studies, experimental mouse models and clinical sample studies have provided evidence for the involvement of TLRs, including TLR2/4, TLR5, TLR3 and TLR7/8/9, in SLE pathogenesis. A number of downstream proteins in the TLR signaling cascade （such as MyD88, IRAKs and IFN-a） are identified as potential therapeutic targets for SLE treatment. Numerous antagonists targeting TLR signaling, including oligonucleotides, small molecular inhibitors and antibodies, are currently under preclinical studies or clinical trials for SLE treatment. Moreover, the emerging new manipulation of TLR signaling by microRNA （miRNA） regulation shows promise for the future treatment of SLE.

关 键 词：systemic lupus erythematosus autoimmune diseases Toll-like receptors TLR antagonists immune modulatoryoligonucieotides small molecular inhibitors ANTIBODIES MIRNAS 

分 类 号：Q78[生物学—分子生物学] Q257