Tolerogenic function of Blimp-1 in dendritic cells.
Tolerogenic function of Blimp-1 in dendritic cells.
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DOI：
10.1084/jem.20110658
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发表时间：
2011-10-24
期刊：
影响因子：
--
通讯作者：
Diamond B
中科院分区：
文献类型：
--
作者：
Kim SJ;Zou YR;Goldstein J;Reizis B;Diamond B
Blimp-1在DC中的表达减少会导致雌性小鼠产生狼疮样自身抗体，而雄性小鼠则不会，这是由于IL-6增加导致生发中心反应增强所致。BLIMP-1被认为是B细胞浆细胞分化和T细胞效应/记忆功能的关键调节因子。我们证明，树突状细胞(DC)中的Blimp-1是维持雌性小鼠免疫耐受所必需的，而不是雄性小鼠。在DC中缺乏Blimp-1表达的雌性小鼠(DCBlimp-1KO)或表达Blimp-1的单倍体小鼠表现出正常的DC发育，但DC功能改变，并产生狼疮样自身抗体。尽管树突状细胞与狼疮的发病机制有关，但以前尚未发现树突状细胞功能缺陷会导致疾病的发生。BLIMP-1KO DC在体外可促进IL-6的产生，并优先诱导滤泡T辅助细胞(TFH细胞)分化。在体内，TFH细胞的扩张与生发中心(GC)反应增强和自身反应性的发展有关。这些研究表明Blimp-1在DC的耐受功能中起着关键作用，并表明DC中Blimp-1的表达减弱可导致适应性免疫系统的异常激活，并以性别特异性的方式发展成狼疮样血清学。这项研究特别令人感兴趣，因为Blimp-1的多态性与SLE有关。
Diminished expression of Blimp-1 in DCs results in the development of lupus-like autoantibodies in female mice, but not male mice, as a result of increased IL-6 driving enhanced germinal center responses. Blimp-1 has been identified as a key regulator of plasma cell differentiation in B cells and effector/memory function in T cells. We demonstrate that Blimp-1 in dendritic cells (DCs) is required to maintain immune tolerance in female but not male mice. Female mice lacking Blimp-1 expression in DCs (DCBlimp-1ko) or haploid for Blimp-1 expression exhibit normal DC development but an altered DC function and develop lupus-like autoantibodies. Although DCs have been implicated in the pathogenesis of lupus, a defect in DC function has not previously been shown to initiate the disease process. Blimp-1ko DCs display increased production of IL-6 and preferentially induce differentiation of follicular T helper cells (TFH cells) in vitro. In vivo, the expansion of TFH cells is associated with an enhanced germinal center (GC) response and the development of autoreactivity. These studies demonstrate a critical role for Blimp-1 in the tolerogenic function of DCs and show that a diminished expression of Blimp-1 in DCs can result in aberrant activation of the adaptive immune system with the development of a lupus-like serology in a gender-specific manner. This study is of particular interest because a polymorphism of Blimp-1 associates with SLE.
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DOI：
10.1126/science.1176676
发表时间：
2009-08-21
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Nurieva RI;Chung Y;Martinez GJ;Yang XO;Tanaka S;Matskevitch TD;Wang YH;Dong C
通讯作者：
Dong C
影响因子：
56.9
作者：
Garside, P;Ingulli, E;Jenkins, MK
通讯作者：
Jenkins, MK
影响因子：
7
作者：
Shlomchik MJ
通讯作者：
Shlomchik MJ
中国汉族人群的全基因组关联研究确定了系统性红斑狼疮的九个新易感位点
影响因子：
30.8
作者：
Han, Jian-Wen;Zheng, Hou-Feng;Zhang, Xue-Jun
通讯作者：
Zhang, Xue-Jun
影响因子：
15.3
作者：
Iwakoshi, Neal N.;Pypaert, Marc;Glimcher, Laurie H.
通讯作者：
Glimcher, Laurie H.