Fujian Provincial Key Laboratory of Transplant Biology, Dongfang Hospital (900th Hospital of the Joint Logistics Team), Xiamen University, China.
Laboratory of Basic Medicine, Fuzhou General Clinical College, Fujian Medical University, China.
Cell Transplant. 2021 Jan-Dec;30:963689721995458. doi: 10.1177/0963689721995458.
Immune cell infiltration plays an important role in the pathophysiology of kidney grafts, but the composition of immune cells is ill-defined. Here, we aimed at evaluating the levels and composition of infiltrating immune cells in kidney grafts. We used CIBERSORT, an established algorithm, to estimate the proportions of 22 immune cell types based on gene expression profiles. We found that non-rejecting kidney grafts were characteristic with high rates of M2 macrophages and resting mast cells. The proportion of M1 macrophages and activated NK cells were increased in antibody-mediated rejection (ABMR). In T cell-mediated rejection (TCMR), a significant increase in CD8 T cell and γδT cell infiltration was observed. CD8 positive T cells were dramatically increased in mixed-ABMR/TCMR. Then, the function of ABMR and TCMR prognostic molecular biomarkers were identified. Finally, we described the gene expression of molecular markers for ABMR diagnosis was elevated and related to the ratio of monocytes and M1 macrophages in ABMR biopsies, while the expression of TCMR diagnosis markers was increased too and positively correlated with γδT cells and activated CD4 memory T cells in TCMR biopsies. Our data suggest that CIBERSORT's deconvolution analysis of gene expression data provides valuable information on the composition of immune cells in renal allografts.
免疫细胞浸润在肾移植的病理生理学中起着重要作用,但免疫细胞的组成尚不清楚。在这里,我们旨在评估肾移植中浸润免疫细胞的水平和组成。我们使用 CIBERSORT,一种已建立的算法,根据基因表达谱来估计 22 种免疫细胞类型的比例。我们发现,无排斥反应的肾移植以高比例的 M2 巨噬细胞和静止肥大细胞为特征。抗体介导的排斥反应(ABMR)中 M1 巨噬细胞和活化 NK 细胞的比例增加。在 T 细胞介导的排斥反应(TCMR)中,观察到 CD8 T 细胞和 γδT 细胞浸润的显著增加。在混合 ABMR/TCMR 中,CD8 阳性 T 细胞显著增加。然后,确定了 ABMR 和 TCMR 预后分子生物标志物的功能。最后,我们描述了 ABMR 诊断的分子标志物的基因表达升高,并与 ABMR 活检中单核细胞和 M1 巨噬细胞的比例相关,而 TCMR 诊断标志物的表达也升高,并与 TCMR 活检中 γδT 细胞和活化的 CD4 记忆 T 细胞呈正相关。我们的数据表明,CIBERSORT 对基因表达数据的去卷积分析提供了有关肾移植中免疫细胞组成的有价值信息。