Interferon-α accelerates murine systemic lupus erythematosus in a T cell-dependent manner.
Interferon-α accelerates murine systemic lupus erythematosus in a T cell-dependent manner.
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DOI：
10.1002/art.30087
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发表时间：
2011-01
影响因子：
--
通讯作者：
Davidson, Anne
中科院分区：
文献类型：
--
作者：
Liu, Zheng;Bethunaickan, Ramalingam;Huang, Weiqing;Lodhi, Umairullah;Solano, Ingrid;Madaio, Michael P.;Davidson, Anne
目的：探讨干扰素α加速狼疮的作用机制。用表达干扰素α的腺病毒治疗NZB/W小鼠。在一些带有抗CD4抗体的小鼠中，T细胞被耗尽。用ELISA法和ELISpot法检测抗dsDNA抗体的产生。免疫荧光染色显示脾组织中生发中心和抗体分泌细胞(ASCs)，肾组织中免疫球蛋白G沉积和白细胞浸润。采用流式细胞仪检测脾细胞表型。最后，用单细胞聚合酶链式反应研究了重链可变区IgG2a和IgG3的体细胞超突变和基因利用。NZB/W小鼠干扰素α加速狼疮与血清中抗双链DNA抗体IgG2和IgG3水平升高以及脾中大量不能发育为长寿命浆细胞的免疫球蛋白ASCs有关。此外，这些小鼠的IgG2a和IgG3抗体是高度体细胞突变的，并使用不同的VH基因谱系。这些小鼠系统性红斑狼疮的诱导与B细胞TLR7表达增加、血清BAFF、IL-6和肿瘤坏死因子α水平升高以及T细胞表达IL-21有关。尽管干扰素α可使血清免疫球蛋白水平升高，但自身抗体的诱导和肾炎的发展都完全依赖于CD4T细胞的帮助。我们的研究表明，尽管干扰素α能激活NZB/W小鼠的先天免疫反应和获得性免疫反应，但CD4T细胞是干扰素α诱导抗双链DNA抗体和临床系统性红斑狼疮所必需的。
To investigate the mechanism for lupus acceleration by interferon alpha (IFNα) in NZB/W mice. NZB/W mice were treated with an adenovirus expressing IFNα. T cells were depleted in some mice with an anti-CD4 antibody. The production of anti-dsDNA antibodies was measured by ELISA and ELISpot assays. Germinal centers and antibody-secreting cells (ASCs) in spleens and IgG deposition and leukocyte infiltrates in kidneys were visualized by immunofluorescence staining. The phenotype of splenic cells was determined by flow cytometry. Finally, somatic hypermutation and gene usage in heavy chain variable regions of IgG2a and IgG3 were studied by single cell PCR. IFNα accelerated lupus in NZB/W mice is associated with elevated serum levels of IgG2 and IgG3 anti-dsDNA antibodies, and accumulation of many IgG ASCs in the spleen, which do not develop into long-lived plasma cells. Furthermore, IgG2a and IgG3 antibodies in these mice are highly somatically mutated and use distinct repertoires of VH genes. The induction of SLE in these mice is associated with an increase in B cell TLR7 expression, increased serum levels of BAFF, IL-6 and TNFα, and induction of T cells expressing IL-21. Although IFNα drives a T-independent increase in serum levels of IgG, autoantibody induction and the development of nephritis are both completely dependent on CD4 T cell help. Our study shows that although IFNα activates both innate and adaptive immune responses in NZB/W mice, CD4 T cells are necessary for IFNα driven induction of anti-dsDNA antibodies and clinical SLE.
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影响因子：
2.9
作者：
Jiang, XiuPing;Suzuki, Hirotatsu;Nakano, Hideo
通讯作者：
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影响因子：
19.6
作者：
Adalid-Peralta, L.;Mathian, A.;Koutouzov, S.
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32.4
作者：
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通讯作者：
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影响因子：
5.4
作者：
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通讯作者：
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影响因子：
4.4
作者：
Heer, Alex K.;Shamshiev, Abdijapar;Marsland, Benjamin J.
通讯作者：
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