title: Role of Toll-like receptors and retinoic acid inducible gene I in endogenous production of type I interferon in dermatomyositis.
abstract: To explore the possible mechanisms implicated in the endogenous production of type I interferons within the muscle tissue of dermatomyositis (DM) patients. We detected the co-localization of plasmacytoid dendritic cells (pDCs) with Toll-like receptors (TLRs) and retinoic acid inducible gene (RIG)-I by immunohistochemistry and immunofluorescence. Western blotting confirmed the expression of TLRs and RIG-I. TLR-3 and RIG-I was preferentially expressed in the perifascicular atrophy fibers of DM. TLR-7 was only in inflammatory infiltrates of a few DM patients. TLR-4 and TLR-9 was expressed mainly in inflammatory infiltrates. Immunofluorescence showed extensive co-localization of BDCA-2 with TLR-9 and little co-localization with TLR-7. Western blotting showed upregulation of expression of TLRs and RIG-I in DM compared with the controls. Our findings indicate that endogenous production of type I IFN in DM is generated by pDCs, mainly through the TLR-9 pathway and in part by TLR-7. TLR-3 and RIG-I are implicated in the formation of perifascicular atrophy in DM.
authors.affiliation: Department of Neurology and Neuromuscular Center, Qilu Hospital of Shandong University, Jinan, China; Department of Neurology, Qilu Hospital of Shandong University, Qingdao, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Neurology and Neuromuscular Center, Qilu Hospital of Shandong University, Jinan, China.
authors.forename: Tingjun
authors.initials: T
authors.lastname: Dai
authors.affiliation: Department of Neurology and Neuromuscular Center, Qilu Hospital of Shandong University, Jinan, China.
authors.forename: Jingwei
authors.initials: J
authors.lastname: Lv
authors.affiliation: Department of Neurology and Neuromuscular Center, Qilu Hospital of Shandong University, Jinan, China.
authors.forename: Kunqian
authors.initials: K
authors.lastname: Ji
authors.affiliation: Department of Neurology and Neuromuscular Center, Qilu Hospital of Shandong University, Jinan, China.
authors.forename: Junling
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Neurology and Neuromuscular Center, Qilu Hospital of Shandong University, Jinan, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Neurology and Neuromuscular Center, Qilu Hospital of Shandong University, Jinan, China; Brain Science Research Institute, Shandong University, Jinan, China. Electronic address: chuanzhuyan@163.com.
authors.forename: Chuanzhu
authors.initials: C
authors.lastname: Yan
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000502:physiology*; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism*; D003882:Dermatomyositis / Q000175:diagnosis* / Q000276:immunology / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007370:Interferon Type I / Q000096:biosynthesis* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011971:Receptors, Immunologic; D012189:Retrospective Studies; D051193:Toll-Like Receptors / Q000502:physiology*; D055815:Young Adult
chemical_list: D007370:Interferon Type I; D011971:Receptors, Immunologic; D051193:Toll-Like Receptors; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases
keywords: Dermatomyositis; Plasmacytoid dendritic cells; Retinoic acid inducible gene I; Toll-like receptor; Type I interferons