Single-cell and bulk RNA sequencing highlights the role of M1-like infiltrating macrophages in antibody-mediated rejection after kidney transplantation

作者全名：Pang, Qidan; Chen, Liang; An, Changyong; Zhou, Juan; Xiao, Hanyu

作者地址：[Pang, Qidan; Zhou, Juan] Chongqing Med Univ, Bishan Hosp, Dept Nephrol, Chongqing 402760, Peoples R China; [Chen, Liang; An, Changyong; Xiao, Hanyu] Chongqing Med Univ, Dept Gen Surg Gastrointestinal Surg, Bishan Hosp, Chongqing 402760, Peoples R China

通信作者：Zhou, J (通讯作者)，Chongqing Med Univ, Bishan Hosp, Dept Nephrol, Chongqing 402760, Peoples R China.; Xiao, HY (通讯作者)，Chongqing Med Univ, Dept Gen Surg Gastrointestinal Surg, Bishan Hosp, Chongqing 402760, Peoples R China.

来源：HELIYON

ESI学科分类：　

WOS号：WOS:001250938000001

JCR分区：Q1

影响因子：3.4

年份：2024

卷号：10

期号：6

开始页：　

结束页：　

文献类型：Article

关键词：Macrophage; Antibody -mediated rejection; Single -cell; Kidney transplantation; Graft loss; Biopsies for cause; STAT1; MIF; PARP9

摘要：Background: Antibody -mediated rejection (ABMR) significantly affects transplanted kidney survival, yet the macrophage phenotype, ontogeny, and mechanisms in ABMR remain unclear. Method: We analyzed post -transplant sequencing and clinical data from GEO and ArrayExpress. Using dimensionality reduction and clustering on scRNA-seq data, we identified macrophage subpopulations and compared their infiltration in ABMR and non -rejection cases. Cibersort quantified these subpopulations in bulk samples. Cellchat, SCENIC, monocle2, and monocle3 helped explore intercellular interactions, predict transcription factors, and simulate differentiation of cell subsets. The Scissor method linked macrophage subgroups with transplant prognosis. Furthermore, hdWGCNA, nichnet, and lasso regression identified key genes associated with core transcription factors in selected macrophages, validated by external datasets. Results: Six macrophage subgroups were identified in five post -transplant kidney biopsies. M1 -like infiltrating macrophages, prevalent in ABMR, correlated with pathological injury severity. MIF acted as a primary intercellular signal in these macrophages. STAT1 regulated monocyte-to-M1like phenotype transformation, impacting transplant prognosis via the IFN gamma pathway. The prognostic models built on the upstream and downstream genes of STAT1 effectively predicted transplant survival. The TLR4-STAT1-PARP9 axis may regulate the pro -inflammatory phenotype of M1 -like infiltrating macrophages, identifying PARP9 as a potential target for mitigating ABMR inflammation. Conclusion: Our study delineates the macrophage landscape in ABMR post -kidney transplantation, underscoring the detrimental impact of M1 -like infiltrating macrophages on ABMR pathology and prognosis.

基金机构：Social Livelihood Field Science and Technology project of Bishan District Science and Technology Bureau [BSKJ2022018]

基金资助正文：<BOLD>Funding</BOLD> This work was supported by Social Livelihood Field Science and Technology project of Bishan District Science and Technology Bureau (BSKJ2022018) .