Single-cell RNA-sequencing reveals distinct immune cell subsets and signaling pathways in IgA nephropathy.
Single-cell RNA-sequencing reveals distinct immune cell subsets and signaling pathways in IgA nephropathy.
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单细胞 RNA 测序揭示 IgA 肾病中独特的免疫细胞亚群和信号通路
DOI：
10.1186/s13578-021-00706-1
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发表时间：
2021-12-11
影响因子：
7.5
通讯作者：
Yang Q
中科院分区：
文献类型：
--
作者：
Zeng H;Wang L;Li J;Luo S;Han Q;Su F;Wei J;Wei X;Wu J;Li B;Huang J;Tang P;Cao C;Zhou Y;Yang Q
IgA肾病是全球最常见的原发性肾小球肾炎。越来越多的证据表明，宿主免疫在IgAN的发生发展中具有重要作用，但其在IgAN早期的动态变化仍不清楚。在这里，我们通过对外周血单核细胞进行单细胞RNA测序(scRNA-seq)，成功地解决了IgAN免疫细胞的早期转录变化。对照组和IgAN患者差异表达基因主要集中在NK细胞介导的细胞毒作用和细胞杀伤途径上。有趣的是，我们发现IgAN患者的NK细胞数量和细胞毒作用显著降低，NK细胞数量和标志基因与临床参数，包括尿蛋白肌酐比值(UPCR)、血清半乳糖缺乏的IgA1和IgA水平呈负相关。一个独特的B细胞亚群，它抑制了NFκB信号，在IgAN中占主导地位，并与疾病进展呈正相关。此外，B细胞的DEGS在不同的病毒感染途径中也得到了丰富。典型单核细胞在IgAN中也有明显改变，表达干扰素诱导基因的单核细胞亚群与IgAN的临床严重程度呈正相关。最后，我们确定了免疫球蛋白肾病细胞间通讯的巨大动力学。我们在单细胞分辨率下解剖了IgAN的免疫格局，为开发新的生物标志物和治疗肾小球肾炎提供了新的见解。网上版载有补充材料，可在10.1186/s13578-021-00706-1查阅。
IgA nephropathy (IgAN) is the most common primary glomerulonephritis globally. Increasing evidence suggests the importance of host immunity in the development of IgAN, but its dynamics during the early stage of IgAN are still largely unclear. Here we successfully resolved the early transcriptomic changes in immune cells of IgAN by conducting single-cell RNA-sequencing (scRNA-seq) with peripheral blood mononuclear cells. The differentially expressed genes (DEGs) between control and IgAN were predominantly enriched in NK cell-mediated cytotoxicity and cell killing pathways. Interestingly, we discovered that the number and cytotoxicity of NK cells are significantly reduced in IgAN patients, where both the number and marker genes of NK cells were negatively associated with the clinical parameters, including the levels of urine protein creatinine ratio (UPCR), serum galactose-deficient IgA1 and IgA. A distinctive B cell subset, which had suppressed NFκB signaling was predominantly in IgAN and positively associated with disease progression. Moreover, the DEGs of B cells were enriched in different viral infection pathways. Classical monocytes also significantly changed in IgAN and a monocyte subset expressing interferon-induced genes was positively associated with the clinical severity of IgAN. Finally, we identified vast dynamics in intercellular communications in IgAN. We dissected the immune landscape of IgAN at the single-cell resolution, which provides new insights in developing novel biomarkers and immunotherapy against glomerulonephritis. The online version contains supplementary material available at 10.1186/s13578-021-00706-1.
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影响因子：
15.9
作者：
CZERKINSKY, C;KOOPMAN, WJ;MESTECKY, J
通讯作者：
MESTECKY, J
影响因子：
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作者：
Feinberg, Mark W.;Wara, Akm Khyrul;Jain, Mukesh K.
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Jain, Mukesh K.
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30.5
作者：
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通讯作者：
Goldman, Daniel H.
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作者：
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影响因子：
2.3
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