Role of innate immunity in a murine model of histidyl–transfer RNA synthetase (Jo‐1)–mediated myositis

Soejima, Makoto; Kang, Eun Ha; Gu, Xinyan; Katsumata, Yasuhiro; Clemens, Paula R.; Ascherman, Dana P.

doi:10.1002/art.30113

Cited by 52 publications

(52 citation statements)

References 17 publications

(26 reference statements)

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“…Many of the self-complementary stimulatory RNAs analyzed in the current study are associated with such conditions. For example, the Jo-1 autoantigen (histidyltRNA synthetase), targeted in patients with polymyositis, has been shown to stimulate the innate immune system (46). TLR3 activation in muscle cells appears to play a role in polymyositis.…”

Section: Discussionmentioning

confidence: 99%

Activation of Autoreactive B Cells by Endogenous TLR7 and TLR3 RNA Ligands

Green

Moody

Debatis

et al. 2012

Journal of Biological Chemistry

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Background: Low affinity autoreactive B cells are activated by co-engagement of the BCR and TLRs. Results: Endogenous RNAs that are associated with autoantigens are ligands for TLR7 and TLR3. Conclusion: Sequence and structure of RNA determines recognition by TLRs. Significance: B cells are activated by RNA delivered through the BCR, and the sequences of RNAs define their stimulatory capacity as TLR ligands.

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Section: Discussionmentioning

confidence: 99%

Activation of Autoreactive B Cells by Endogenous TLR7 and TLR3 RNA Ligands

Green

Moody

Debatis

et al. 2012

Journal of Biological Chemistry

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“…In contrast, HisRS(61-509), which lacks the first 60 aa, failed to stimulate these inflammation-related cell migration events (8). Other in vivo studies in mice suggest that HisRS has an etiological relationship to the disease (10).…”

Section: Idiopathic Inflammatory Myositis (Iim)mentioning

confidence: 96%

Secreted Histidyl-tRNA Synthetase Splice Variants Elaborate Major Epitopes for Autoantibodies in Inflammatory Myositis

Zhou

Wang

et al. 2014

Journal of Biological Chemistry

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Background: Autoantibodies (anti-Jo-1) to cytoplasmic histidyl-tRNA synthetase (HisRS) are associated with inflammatory myositis. Results: HisRS and two splice variants (SVs) cross-react with anti-Jo-1 antibodies and are secreted; at least one SV transcript is up-regulated in dermatomyositis. Conclusion: Secreted HisRS SVs contain major epitopes of anti-Jo-1 autoantibodies. Significance: Secreted HisRS and its SVs share epitopes for potential extracellular anti-Jo-1 antibody binding.

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“…Additionally, aminoacyltRNA synthetases function as signaling molecules, enhancing tumor necrosis factor secretion from macrophages [17]. Following intramuscular immunization in a recent murine model, histidyl-tRNA synthetase induced both early (7 days) and sustained (7 weeks) inflammatory responses independent of B-cell receptor, T-cell receptor, and Toll-like receptor 4 signaling, suggesting involvement of both innate and adaptive immune responses [18].…”

Section: Antisynthetase Autoantibodiesmentioning

confidence: 99%

Antisynthetase Syndrome

2011

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Autoantibodies to eight of the aminoacyl-transfer RNA synthetases-the most well-recognized of which is anti-histidyl (Jo-1)-have all been implicated in the pathogenesis of antisynthetase syndrome (AS). AS is characterized by varying degrees of interstitial lung disease, myositis, arthropathy, fever, Raynaud's phenomenon, and mechanic's hands, and the morbidity and mortality of the disease are usually linked to the pulmonary findings. The value of a lung biopsy in AS cannot be overemphasized, as it serves to describe the underlying etiology of the interstitial lung disease, guide therapy, and estimate prognosis. Muscle disease shares many clinical features of polymyositis, yet histologically, the inflammatory involvement resembles that of dermatomyositis. Because inflammatory arthritis mimics rheumatoid arthritis, AS should be considered in atypical cases. Corticosteroids are the mainstay of acute therapy, although treatment often requires immunosuppressant medications such as cyclophosphamide, azathioprine, mycophenolate mofetil, cyclosporine, tacrolimus, or rituximab.

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Role of innate immunity in a murine model of histidyl–transfer RNA synthetase (Jo‐1)–mediated myositis

Abstract: Conclusion. Collectively, the findings of these experiments support a model in which HisRS can trigger both innate and adaptive immune responses that culminate in severe muscle inflammation that is the hallmark of idiopathic inflammatory myopathy.

Cited by 52 publications

References 17 publications

Activation of Autoreactive B Cells by Endogenous TLR7 and TLR3 RNA Ligands

Activation of Autoreactive B Cells by Endogenous TLR7 and TLR3 RNA Ligands

Secreted Histidyl-tRNA Synthetase Splice Variants Elaborate Major Epitopes for Autoantibodies in Inflammatory Myositis

Antisynthetase Syndrome

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