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Frontiers in Immunology: CRAC通道控制狼疮性肾炎病原性B细胞的分化

2021-11-11 彼岸河边草 MedSci原创

分化狼疮性肾炎B细胞钙通道
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该研究主要探究CRAC通道控制致病B细胞的分化并促进狼疮性肾炎的进展。

      背景：Ca2+释放激活(CRAC)通道是淋巴细胞中主要的Ca2+流入途径，对免疫反应至关重要。狼疮性肾炎(LN)是一种自身免疫性疾病，其特征是由于免疫耐受的广泛丧失而产生自身抗体。

      方法和结果：在这项研究中，RNA-seq分析显示，LN患者的幼稚B细胞中钙跨膜转运和钙通道活性增强。通过流式细胞术和蛋白质印迹证实了LN患者的初始B细胞中ORAI1、ORAI2和STIM2（三者均是CRAC的组成成分）的表达增加，这意味着CRAC通道在LN B细胞失调中可能具有一定作用。在体外研究中，YM-58483对CRAC通道的抑制或ORAI1特异性小干扰RNA (siRNA)的下调降低了Ca2+/钙调蛋白依赖性蛋白激酶2 (CaMK2)的磷酸化并抑制了人B细胞中的Blimp-1表达，导致B细胞分化和免疫球蛋白G (IgG)产生减少。用CaMK2特异性siRNA处理的B细胞显示出浆细胞分化和IgG产生的缺陷。在体内研究中，YM-58483不仅改善了LN的进展，还阻止了LN的发展。用YM-58483治疗的MRL/lpr狼疮小鼠的脾脏中浆细胞百分比较低，血清中抗双链DNA抗体的浓度显著降低。重要的是，用YM-58483治疗的小鼠肾小球免疫沉积减少并减轻了肾脏损伤，这在NZM2328狼疮小鼠中得到了进一步证实。

     结论：CRAC通道控制了致病B细胞的分化并促进了LN的进展。这项研究提供了对LN发病机制的见解，并且CRAC通道可以作为LN的潜在治疗靶点。

出处：

Li X, Zeng Q, Wang S, Li M, Chen X, Huang Y, Chen B, Zhou M, Lai Y, Guo C, Zhao S, Zhang H, Yang N. CRAC Channel Controls the Differentiation of Pathogenic B Cells in Lupus Nephritis. Front Immunol. 2021 Oct 22;12:779560. doi: 10.3389/fimmu.2021.779560. PMID: 34745151; PMCID: PMC8569388.

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    2022-01-12 anminleiryan

    #ERS#

    0

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    2021-11-12 xiaoyeshuang

    #B细胞#

    0

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    2021-11-12 sunrural_42825357

    #狼疮#

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    2021-11-12 villahu

    #肾炎#

    0

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