Role of nucleic acid-sensing TLRs in diverse autoantibody specificities and anti-nuclear antibody-producing B cells.
Role of nucleic acid-sensing TLRs in diverse autoantibody specificities and anti-nuclear antibody-producing B cells.
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DOI：
10.4049/jimmunol.1202986
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发表时间：
2013-05-15
期刊：
影响因子：
--
通讯作者：
Kono DH
中科院分区：
文献类型：
--
作者：
Koh YT;Scatizzi JC;Gahan JD;Lawson BR;Baccala R;Pollard KM;Beutler BA;Theofilopoulos AN;Kono DH
核酸（NA）敏感TLRs （NA-TLRs）促进系统性红斑狼疮抗核抗体的诱导。然而，在狼疮和其他自身免疫性疾病中发生的其他非核致病性自身抗体特异性在多大程度上依赖于na - tlr，以及在系统性自身免疫中哪些免疫细胞需要na - tlr，这些仍有待确定。使用缺乏NA-TLR信号的Unc93b13d狼疮易感小鼠，我们发现所有致病的非核自身抗体特异性，甚至抗红细胞，都需要NA-TLR。此外，我们证明了B细胞中的na - tlr是抗染色质和类风湿因子发展所必需的。这些发现支持了一种统一的na - tlr介导的自身抗体产生机制，该机制对系统性红斑狼疮和其他几种体液介导的自身免疫性疾病具有病理生理和治疗意义。特别是，我们的研究结果表明，仅以B细胞中的NA-TLR信号为靶点就足以特异性地阻断多种自身抗体的产生。
Nucleic acid (NA)–sensing TLRs (NA-TLRs) promote the induction of anti-nuclear Abs in systemic lupus erythematosus. However, the extent to which other nonnuclear pathogenic autoantibody specificities that occur in lupus and independently in other autoimmune diseases depend on NA-TLRs, and which immune cells require NA-TLRs in systemic autoimmunity, remains to be determined. Using Unc93b13d lupus-prone mice that lack NA-TLR signaling, we found that all pathogenic nonnuclear auto-antibody specificities examined, even anti-RBC, required NA-TLRs. Furthermore, we document that NA-TLRs in B cells were required for the development of antichromatin and rheumatoid factor. These findings support a unifying NA-TLR–mediated mechanism of autoantibody production that has both pathophysiological and therapeutic implications for systemic lupus erythematosus and several other humoral-mediated autoimmune diseases. In particular, our findings suggest that targeting of NA-TLR signaling in B cells alone would be sufficient to specifically block production of a broad diversity of autoantibodies.
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DOI：
10.4049/jimmunol.1000698
发表时间：
2010-07-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
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作者：
Aït-Azzouzene D;Kono DH;Gonzalez-Quintial R;McHeyzer-Williams LJ;Lim M;Wickramarachchi D;Gerdes T;Gavin AL;Skog P;McHeyzer-Williams MG;Nemazee D;Theofilopoulos AN
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32.4
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10.4049/jimmunol.1202195
发表时间：
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期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
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影响因子：
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DOI：
10.4049/jimmunol.1003911
发表时间：
2011-08-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
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