Early, transient depletion of plasmacytoid dendritic cells ameliorates autoimmunity in a lupus model.
Early, transient depletion of plasmacytoid dendritic cells ameliorates autoimmunity in a lupus model.
复制标题
DOI：
10.1084/jem.20132620
复制
发表时间：
2014-09-22
期刊：
影响因子：
--
通讯作者：
Colonna M
中科院分区：
文献类型：
--
作者：
Rowland SL;Riggs JM;Gilfillan S;Bugatti M;Vermi W;Kolbeck R;Unanue ER;Sanjuan MA;Colonna M
短暂的基因消除称为浆细胞样树突状细胞（pDC）的特殊细胞群可以逆转小鼠狼疮的许多特征。疾病减少部分归因于称为干扰素的炎症分子表达的减少，干扰素主要由 pDC 产生。浆细胞样树突状细胞（pDC）长期以来一直与狼疮的发病机制有关。然而，这一结论很大程度上基于 pDC 大量产生 IFN-α/β 与人类狼疮患者中常见的 IFN-α/β“特征”之间的相关性。 pDC 对体内疾病的具体贡献尚未得到详细研究。为此，我们培育了一种 BXSB 狼疮易感小鼠品系，其中 pDC 可以在体内选择性地耗尽。在疾病发生前早期短暂消融 pDC 可减少脾肿大和淋巴结肿大、T 细胞和 B 细胞的扩增和活化受损、抗核自身抗原的抗体减少并改善肾脏病理学。病理学的改善与组织中 IFN-α/β 诱导基因转录的减少同时发生。 PDC 耗竭对免疫细胞的激活有直接影响，重要的是，即使 pDC 后来恢复，对病理学的有益影响仍然持续，这表明 pDC 早期对疾病有贡献。总之，我们的研究结果证明了 pDC 在 IFN-α/β 依赖性自身免疫性狼疮起始过程中发挥着关键作用，并表明 pDC 是治疗 SLE 的一个有吸引力的治疗靶点。
Transient, genetic elimination of a specialized group of cells called plasmacytoid dendritic cells (pDCs) reverses many features of lupus in mice. Disease reduction was attributed in part to decreased expression of inflammatory molecules called interferons, which are produced primarily by pDCs. Plasmacytoid dendritic cells (pDCs) have long been implicated in the pathogenesis of lupus. However, this conclusion has been largely based on a correlative link between the copious production of IFN-α/β by pDCs and the IFN-α/β “signature” often seen in human lupus patients. The specific contribution of pDCs to disease in vivo has not been investigated in detail. For this reason, we generated a strain of BXSB lupus-prone mice in which pDCs can be selectively depleted in vivo. Early, transient ablation of pDCs before disease initiation resulted in reduced splenomegaly and lymphadenopathy, impaired expansion and activation of T and B cells, reduced antibodies against nuclear autoantigens and improved kidney pathology. Amelioration of pathology coincided with decreased transcription of IFN-α/β–induced genes in tissues. PDC depletion had an immediate impact on the activation of immune cells, and importantly, the beneficial effects on pathology were sustained even though pDCs later recovered, indicating an early pDC contribution to disease. Together, our findings demonstrate a critical function for pDCs during the IFN-α/β–dependent initiation of autoimmune lupus and point to pDCs as an attractive therapeutic target for the treatment of SLE.
登录
查看更多内容
影响因子：
12.8
作者：
Goules, Andreas;Tzioufas, Athanasios G.;Routsias, John G.
通讯作者：
Routsias, John G.
影响因子：
20.3
作者：
Hao, Yi;O'Neill, Patrick;Cancro, Michael P.
通讯作者：
Cancro, Michael P.
DOI：
10.4049/jimmunol.1201477
发表时间：
2012-12-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Baccala R;Gonzalez-Quintial R;Schreiber RD;Lawson BR;Kono DH;Theofilopoulos AN
通讯作者：
Theofilopoulos AN
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
DOI：
10.1038/nri3383
发表时间：
2013-02
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--