Functional redundancy of MyD88-dependent signaling pathways in a murine model of histidyl-transfer RNA synthetase-induced myositis.
Functional redundancy of MyD88-dependent signaling pathways in a murine model of histidyl-transfer RNA synthetase-induced myositis.
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DOI：
10.4049/jimmunol.1203070
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发表时间：
2013-08-15
期刊：
影响因子：
--
通讯作者：
Ascherman DP
中科院分区：
文献类型：
--
作者：
Fernandez I;Harlow L;Zang Y;Liu-Bryan R;Ridgway WM;Clemens PR;Ascherman DP
We have previously shown that intramuscular 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−/− and B6.TLR4−/− single knockout mice yielded significant lymphocytic infiltration of muscle tissue comparable to that produced in C57BL/6 WT mice. In contrast, concomitant elimination of TLR2 and TLR4 signaling in B6.TLR2−/−.TLR4−/− double knockout mice markedly reduced the severity of HRS-induced muscle inflammation. Complementary subfragment analysis demonstrated that amino acids 60–90 of HRS were absolutely required for in vitro as well as in vivo signaling via these MyD88-dependent TLR pathways—effects 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.
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影响因子：
--
作者：
Guggino G;Giardina AR;Ciccia F;Triolo G;Dieli F;Sireci G
通讯作者：
Sireci G
组酰基TRNA合成酶和天冬酰基-TRNA合成酶，肌炎中的自身抗原，激活T淋巴细胞上的趋化因子受体和未成熟的树突状细胞。
影响因子：
15.3
作者：
Howard, O M Zack;Dong, Hui Fang;Yang, De;Raben, Nina;Nagaraju, Kanneboyina;Rosen, Antony;Casciola-Rosen, Livia;Hartlein, Michael;Kron, Michael;Yang, David;Yiadom, Kwabena;Dwivedi, Sunita;Plotz, Paul H;Oppenheim, Joost J
通讯作者：
Oppenheim, Joost J
影响因子：
56.9
作者：
Wakasugi, K;Schimmel, P
通讯作者：
Schimmel, P
DOI：
10.1073/pnas.1120585109
发表时间：
2012-08-07
影响因子：
11.1
作者：
Reynolds, Joseph M.;Martinez, Gustavo J.;Dong, Chen
通讯作者：
Dong, Chen
影响因子：
--
作者：
Eloranta, Maija-Leena;Helmers, Sevim Barbasso;Lundberg, Ingrid E.
通讯作者：
Lundberg, Ingrid E.