Dendritic cells in lupus are not required for activation of T and B cells but promote their expansion, resulting in tissue damage.
Dendritic cells in lupus are not required for activation of T and B cells but promote their expansion, resulting in tissue damage.
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DOI：
10.1016/j.immuni.2010.11.025
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发表时间：
2010-12-14
期刊：
影响因子：
32.4
通讯作者：
Shlomchik MJ
中科院分区：
文献类型：
--
作者：
Teichmann LL;Ols ML;Kashgarian M;Reizis B;Kaplan DH;Shlomchik MJ
树突状细胞(DC)启动和控制针对感染的适应性免疫反应。然而，它们在系统性红斑狼疮等自身免疫性疾病中的抗自身适应性免疫反应中的作用尚不确定。通过结构性地删除MRL.Faslpr小鼠中的DC，我们表明它们在小鼠狼疮中具有复杂的作用。DC缺失的净效果是改善疾病。DC对T细胞的扩增和分化至关重要，但令人惊讶的是，它们的初始激活并不是必需的。相应地，在缺乏DC的情况下，肾间质浸润发展，但未能进展。DC缺失伴随着炎性和调节性T细胞数量的减少。出乎意料的是，浆母细胞数量和自身抗体浓度取决于DC，而不是血清总免疫球蛋白浓度，这表明DC对滤泡外体液反应有影响。这些发现揭示了DC在小鼠狼疮中以意想不到的方式发挥作用，并验证了它们作为自身免疫的潜在治疗靶点的有效性。
Dendritic cells (DCs) initiate and control the adaptive immune response against infections. However, their contributions to the anti-self adaptive immune response in autoimmune disorders like systemic lupus erythematosus are uncertain. By constitutively deleting DCs in MRL.Faslpr mice we show that they have complex roles in murine lupus. The net effect of DC deletion was to ameliorate disease. DCs were crucial for the expansion and differentiation of T cells but, surprisingly, not required for their initial activation. Correspondingly, kidney interstitial infiltrates developed in the absence of DCs, but failed to progress. DC deletion concomitantly decreased inflammatory and regulatory T cell numbers. Unexpectedly, plasmablast numbers and autoantibody concentrations depended on DCs, in contrast to total serum immunoglobulin concentrations, suggesting an effect of DCs on extrafollicular humoral responses. These findings reveal that DCs operate in unanticipated ways in murine lupus and validate them as a potential therapeutic target in autoimmunity.
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DOI：
10.1084/jem.194.6.769
发表时间：
2001-09-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Hawiger D;Inaba K;Dorsett Y;Guo M;Mahnke K;Rivera M;Ravetch JV;Steinman RM;Nussenzweig MC
通讯作者：
Nussenzweig MC
DOI：
10.1084/jem.20062648
发表时间：
2007-07-09
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Caton ML;Smith-Raska MR;Reizis B
通讯作者：
Reizis B
影响因子：
4.4
作者：
Ahuja, Anupama;Shupe, Jonathan;Shlomchik, Mark J.
通讯作者：
Shlomchik, Mark J.
影响因子：
27.4
作者：
Jonsdottir, T.;Gunnarsson, I.;van Vollenhoven, R. F.
通讯作者：
van Vollenhoven, R. F.
影响因子：
6.7
作者：
De Trez C;Magez S;Akira S;Ryffel B;Carlier Y;Muraille E
通讯作者：
Muraille E