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Abstract：
IgA nephropathy (IgAN) is the most common primary glomerulonephritis, characterized by glomerular deposition of IgA immune complexes, mainly produced by B cells under the regulation of CD4+T cells. However, the alterations of specific CD4+T cell subsets and the mechanism of B cells activation in IgAN remain unclear. Therefore, we aimed to investigate the landscape characteristics and role of CD4+T cells in the progression of IgAN. We identified that the proportion of Th2, Th17 and Tfh (follicular helper T) cells in patients with IgAN was significantly higher than that of healthy controls (P < 0.05). Single-cell RNA sequencing of peripheral blood mononuclear cells (PBMCs) showed that Th cells and B cells in patients with IgAN were more activated. Correspondingly, multiplex immunohistochemistry staining of renal biopsy showed increased infiltration of CD4+T and B cells in the kidneys of patients with IgAN. The degree of infiltration was positively correlated with the degree of renal damage. Interestingly, the proportion of Tfh cells in peripheral blood was positively correlated with the severity of proteinuria. Moreover, the proximity position of Tfh cells and B cells suggested that cell-cell interactions between Tfh and B cells were happening in situ. Intercellular communication analysis also showed enhanced interaction between Tfh cells and B cells in IgAN. Our findings suggested that Tfh cells of patients possibly contributed to the progression of IgAN by activating B cells via cell-cell interactions and TNFSF14-TNFRSF14 may be an underlying signaling pathway.
摘要：
IgA肾病（IgAN）是最常见的原发性肾小球肾炎，以IgA免疫复合物的肾小球沉积为特征，主要由CD4+T细胞调节的B细胞产生。然而,IgAN中特异性CD4+T细胞亚群的改变和B细胞活化机制尚不清楚.因此,我们旨在探讨CD4+T细胞在IgAN进展中的景观特征和作用。我们发现，IgAN患者中Th2，Th17和Tfh（滤泡辅助性T）细胞的比例明显高于健康对照组（P<0.05）。外周血单个核细胞（PBMC）的单细胞RNA测序显示，IgAN患者的Th细胞和B细胞更活跃。相应地,肾活检的多重免疫组织化学染色显示IgAN患者肾脏中CD4T和B细胞浸润增加。浸润程度与肾损害程度呈正相关。有趣的是,外周血中Tfh细胞比例与蛋白尿严重程度呈正相关。此外，Tfh细胞和B细胞的接近位置表明Tfh和B细胞之间的细胞相互作用在原位发生。细胞间通讯分析还显示IgAN中Tfh细胞与B细胞之间的相互作用增强。我们的研究结果表明，患者的Tfh细胞可能通过细胞间相互作用激活B细胞而促进IgAN的进展，TNFSF14-TNFRSF14可能是潜在的信号通路。
