TLR7-dependent and FcgammaR-independent production of type I interferon in experimental mouse lupus.
TLR7-dependent and FcgammaR-independent production of type I interferon in experimental mouse lupus.
复制标题
DOI：
10.1084/jem.20080462
复制
发表时间：
2008-12-22
期刊：
影响因子：
--
通讯作者：
Reeves WH
中科院分区：
文献类型：
--
作者：
Lee PY;Kumagai Y;Li Y;Takeuchi O;Yoshida H;Weinstein J;Kellner ES;Nacionales D;Barker T;Kelly-Scumpia K;van Rooijen N;Kumar H;Kawai T;Satoh M;Akira S;Reeves WH
I型干扰素（IFN-I）的产生和IFN-stimulated gene（ISG）的表达增加与系统性红斑狼疮（SLE）的发病机制有关。尽管SLE中IFN-I产生失调的机制尚不清楚，但认为自身抗体介导的内源性核酸摄取起作用。2，6，10，14-四甲基十五烷（TMPD;也称为降植烷）在小鼠中诱导狼疮样疾病，其特征在于具有针对DNA和核糖核蛋白的自身抗体的免疫复合物肾炎。我们最近报道了TMPD还引起ISG表达增加，并且狼疮的发展完全依赖于IFN-I信号传导（Nacionales，D.C.，K.M.凯莉-斯堪皮亚，P.Y.李，J. S.温斯坦河里昂，E. Sobel，M. Satoh和W.H.里夫斯2007. Arthritis Rheum. 56：3770-3783）。我们发现TMPD通过Toll样受体（TLR）7和髓样分化因子88（MyD 88）依赖性途径促进IFN-I产生、单核细胞募集和自身抗体产生。体外研究表明，TMPD增强TLR 7配体的作用，但不直接激活TLR 7本身。TMPD的作用被Y连锁自身免疫加速簇放大，该簇携带TLR 7基因的重复。相反，Fcγ受体（FcγRs）的缺乏不影响IFN-I的产生。总的来说，数据表明TMPD刺激的IFN-I产生需要TLR 7/MyD 88信号传导，并且不依赖于自身抗体介导的Fcγ R对核糖核蛋白的摄取。
Increased type I interferon (IFN-I) production and IFN-stimulated gene (ISG) expression are linked to the pathogenesis of systemic lupus erythematosus (SLE). Although the mechanisms responsible for dysregulated IFN-I production in SLE remain unclear, autoantibody-mediated uptake of endogenous nucleic acids is thought to play a role. 2,6,10,14-tetramethylpentadecane (TMPD; also known as pristane) induces a lupus-like disease in mice characterized by immune complex nephritis with autoantibodies to DNA and ribonucleoproteins. We recently reported that TMPD also causes increased ISG expression and that the development of the lupus is completely dependent on IFN-I signaling (Nacionales, D.C., K.M. Kelly-Scumpia, P.Y. Lee, J.S. Weinstein, R. Lyons, E. Sobel, M. Satoh, and W.H. Reeves. 2007. Arthritis Rheum. 56:3770–3783). We show that TMPD elicits IFN-I production, monocyte recruitment, and autoantibody production exclusively through a Toll-like receptor (TLR) 7– and myeloid differentiation factor 88 (MyD88)–dependent pathway. In vitro studies revealed that TMPD augments the effect of TLR7 ligands but does not directly activate TLR7 itself. The effects of TMPD were amplified by the Y-linked autoimmune acceleration cluster, which carries a duplication of the TLR7 gene. In contrast, deficiency of Fcγ receptors (FcγRs) did not affect the production of IFN-I. Collectively, the data demonstrate that TMPD-stimulated IFN-I production requires TLR7/MyD88 signaling and is independent of autoantibody-mediated uptake of ribonucleoproteins by FcγRs.
登录
查看更多内容
RNA干扰关键组件的自身免疫性靶向。
影响因子：
4.9
作者：
Jakymiw A;Ikeda K;Fritzler MJ;Reeves WH;Satoh M;Chan EK
通讯作者：
Chan EK
影响因子：
32.4
作者：
Berland, Robert;Fernandez, Luis;Imanishi-Kari, Thereza
通讯作者：
Imanishi-Kari, Thereza
影响因子：
30.5
作者：
Kawai, T;Takahashi, K;Akira, S
通讯作者：
Akira, S
DOI：
10.1084/jem.20021553
发表时间：
2003-03-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Bennett L;Palucka AK;Arce E;Cantrell V;Borvak J;Banchereau J;Pascual V
通讯作者：
Pascual V
影响因子：
32.4
作者：
Jego, G;Palucka, AK;Banchereau, J
通讯作者：
Banchereau, J