{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T23:02:36Z","timestamp":1791068556900,"version":"4.1.0"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2013,8,1]],"date-time":"2013-08-01T00:00:00Z","timestamp":1375315200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,8,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>We have previously shown that i.m. administration of bacterially expressed murine histidyl-tRNA synthetase (HRS) triggers florid muscle inflammation (relative to appropriate control proteins) in various congenic strains of mice. Because severe disease develops even in the absence of adaptive immune responses to HRS, we sought to identify innate immune signaling components contributing to our model of HRS-induced myositis. In vitro stimulation assays demonstrated HRS-mediated activation of HEK293 cells transfected with either TLR2 or TLR4, revealing an excitatory capacity exceeding that of other bacterially expressed fusion proteins. Corresponding to this apparent functional redundancy of TLR signaling pathways, HRS immunization of B6.TLR2\u2212\/\u2212 and B6.TLR4\u2212\/\u2212 single-knockout mice yielded significant lymphocytic infiltration of muscle tissue comparable to that produced in C57BL\/6 wild-type mice. In contrast, concomitant elimination of TLR2 and TLR4 signaling in B6.TLR2\u2212\/\u2212.TLR4\u2212\/\u2212 double-knockout mice markedly reduced the severity of HRS-induced muscle inflammation. Complementary subfragment analysis demonstrated that aa 60\u201390 of HRS were absolutely required for in vitro as well as in vivo signaling via these MyD88-dependent TLR pathways\u2014effects mediated, in part, through preferential binding of exogenous ligands capable of activating specific TLRs. Collectively, these experiments indicate that multiple MyD88-dependent signaling cascades contribute to this model of HRS-induced myositis, underscoring the antigenic versatility of HRS and confirming the importance of innate immunity in this system.<\/jats:p>","DOI":"10.4049\/jimmunol.1203070","type":"journal-article","created":{"date-parts":[[2013,7,11]],"date-time":"2013-07-11T00:40:06Z","timestamp":1373503206000},"page":"1865-1872","source":"Crossref","is-referenced-by-count":30,"title":["Functional Redundancy of MyD88-Dependent Signaling Pathways in a Murine Model of Histidyl-Transfer RNA Synthetase\u2013Induced Myositis"],"prefix":"10.1093","volume":"191","author":[{"given":"Irina","family":"Fernandez","sequence":"first","affiliation":[{"name":"Division of Rheumatology, Department of Medicine, University of Miami Miller School of Medicine , Miami, FL 33136"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Harlow","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine, University of Miami Miller School of Medicine , Miami, FL 33136"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunjuan","family":"Zang","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine, University of Miami Miller School of Medicine , Miami, FL 33136"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ru","family":"Liu-Bryan","sequence":"additional","affiliation":[{"name":"Rheumatology Section, Department of Medicine, University of California, San Diego School of Medicine , La Jolla, CA 92093"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William M","family":"Ridgway","sequence":"additional","affiliation":[{"name":"Division of Immunology, Allergy, and Rheumatology, Department of Medicine, University of Cincinnati School of Medicine , Cincinnati, OH 45267"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula R","family":"Clemens","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Pittsburgh School of Medicine , Pittsburgh, PA 15213"},{"name":"Neurology Service, Department of Veterans Affairs Medical Center , Pittsburgh, PA 15240"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dana P","family":"Ascherman","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine, University of Miami Miller School of Medicine , Miami, FL 33136"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2013,8,15]]},"reference":[{"key":"2025032405182600100_r1","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1097\/WCO.0b013e3283311ddf","article-title":"Inflammatory myopathies: disease mechanisms","volume":"22","author":"Greenberg","year":"2009","journal-title":"Curr. 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