Zeng Honghui, Wang Le, Li Jiajia, Luo Siweier, Han Qianqian, Su Fang, Wei Jing, Wei Xiaona, Wu Jianping, Li Bin, Huang Jingang, Tang Patrick, Cao Chunwei, Zhou Yiming, Yang Qiongqiong
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, Guangdong, China.
Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, Guangdong, China.
Cell Biosci. 2021 Dec 11;11(1):203. doi: 10.1186/s13578-021-00706-1.
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.
IgA肾病（IgAN）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IgA肾病发生发展中的重要性，但其在IgA肾病早期阶段的动态变化仍不清楚。
在此，我们通过对外周血单个核细胞进行单细胞RNA测序（scRNA-seq），成功解析了IgA肾病免疫细胞的早期转录组变化。对照组和IgA肾病组之间的差异表达基因（DEGs）主要富集于自然杀伤（NK）细胞介导的细胞毒性和细胞杀伤途径。有趣的是，我们发现IgA肾病患者中NK细胞的数量和细胞毒性显著降低，其中NK细胞的数量和标记基因均与临床参数呈负相关，包括尿蛋白肌酐比值（UPCR）、血清半乳糖缺陷型IgA1和IgA水平。一个抑制NFκB信号传导的独特B细胞亚群在IgA肾病中占主导地位，并与疾病进展呈正相关。此外，B细胞的DEGs富集于不同的病毒感染途径。经典单核细胞在IgA肾病中也有显著变化，一个表达干扰素诱导基因的单核细胞亚群与IgA肾病的临床严重程度呈正相关。最后，我们确定了IgA肾病细胞间通讯的巨大动态变化。
我们以单细胞分辨率剖析了IgA肾病的免疫格局，为开发针对肾小球肾炎的新型生物标志物和免疫疗法提供了新的见解。
