Granulocytic myeloid-derived suppressor cells contribute to IFN-I signaling activation of B cells and disease progression through the lncRNA NEAT1-BAFF axis in systemic lupus erythematosus
Granulocytic myeloid-derived suppressor cells contribute to IFN-I signaling activation of B cells and disease progression through the lncRNA NEAT1-BAFF axis in systemic lupus erythematosus
复制标题
在系统性红斑狼疮中，粒细胞骨髓源性抑制细胞通过 lncRNA NEAT1-BAFF 轴参与 B 细胞的 IFN-I 信号传导激活和疾病进展。
DOI：
10.1016/j.bbadis.2019.165554
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发表时间：
2020-01-01
影响因子：
6.2
通讯作者：
Xiong, Huabao
中科院分区：
文献类型：
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作者：
Dong, Guanjun;Yang, Yonghong;Xiong, Huabao
B细胞中干扰素(IFN)- 1信号的激活与系统性红斑狼疮（SLE）的发病机制有关。最近的研究表明，骨髓源性抑制细胞（MDSCs）在SLE患者和狼疮易感性MRL/lpr小鼠中显著扩增，并参与SLE的发病机制。然而，slel衍生的MDSCs在调节B细胞IFNI信号激活中的作用尚不清楚。在这里，我们证明了MDSCs的扩增，包括粒细胞(G)-MDSCs和单核细胞(M)-MDSCs，在SLE的进展过程中与B细胞的IFN-I信号相关。有趣的是，来自MRL/lpr小鼠的G-MDSCs，而不是M-MDSCs，可以显著促进B细胞的IFN-I信号激活，并参与SLE的发病机制。在机制上，我们发现长链非编码RNA NEAT1在MRL/lpr小鼠的G-MDSCs中过表达，并通过B细胞活化因子（BAFF）分泌诱导G-MDSCs对IFN-I信号通路的激活。重要的是，NEAT1缺乏显著减轻了前列腺素诱导狼疮小鼠的狼疮症状。此外，SLE患者的NEAT1和BAFF与IFN特征呈正相关。总之，G-MDSCs可能通过NEAT1-BAFF轴参与SLE B细胞中的IFN信号，突出G-MDSCs作为治疗SLE的潜在治疗靶点。
Activation of interferon (IFN)-I signaling in B cells contributes to the pathogenesis of systemic lupus erythematosus (SLE). Recent studies have shown that myeloid-derived suppressor cells (MDSCs) significantly expand in SLE patients and lupus-prone MRL/lpr mice and contribute to the pathogenesis of SLE. However, the role of SLE-derived MDSCs in regulating IFNI signaling activation of B cells remains unknown. Here, we demonstrate that expansions of MDSCs, including granulocyte (G)-MDSCs and monocytic (M)-MDSCs, during the progression of SLE were correlated with the IFN-I signature of B cells. Interestingly, G-MDSCs from MRL/lpr mice, but not M-MDSCs, could significantly promote IFN-I signaling activation of B cells and contribute to the pathogenesis of SLE. Mechanistically, we identified that the long non-coding RNA NEAT1 was over-expressed in G-MDSCs from MRL/lpr mice and could induce the promotion of G-MDSCs on IFN-I signaling activation of B cells through B cell-activating factor (BAFF) secretion. Importantly, NEAT1 deficiency significantly attenuated the lupus symptoms in pristane-induced lupus mice. In addition, there was a positive correlation between NEAT1 and BAFF with the IFN signature in SLE patients. In conclusion, G-MDSCs may contribute to the IFN signature in SLE B cells through the NEAT1-BAFF axis, highlighting G-MDSCs as a potential therapeutic target to treat SLE.