Single-cell RNA sequencing analysis reveals the heterogeneity of IL-10 producing regulatory B cells in lupus-prone mice.
Single-cell RNA sequencing analysis reveals the heterogeneity of IL-10 producing regulatory B cells in lupus-prone mice.
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DOI：
10.3389/fimmu.2023.1282770
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发表时间：
2023
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
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作者：
B细胞在包括系统性红斑狼疮（SLE）在内的自身免疫性疾病中可以具有致病和保护作用。产生IL-10的调节性B细胞（BCLs）的数量或免疫抑制功能的缺陷可导致加重的自身免疫性炎症。然而，确切的作用，狼疮发病机制中的贝伐他汀尚未阐明。我们通过scRNA-seq进行了基因表达分析，以表征狼疮易感小鼠疾病进展各阶段脾脏布雷格亚群和分子谱的差异。通过表型分析证实了来自患有活动性疾病的小鼠的BclB中基于转录组的变化。我们发现，边缘区（MZ）谱系Bcl 2的丢失，浆母细胞/浆细胞（PB-PC）谱系Bcl 2的增加，以及炎症基因特征的总体增加是活动性疾病的特征，与疾病前阶段的Bcl 2相比。然而，在活动性疾病小鼠中，表达IL-10的MZ Bp 53和PB-PC的频率均显著降低。总体而言，我们已经确定了与活动性疾病相关的布雷格亚群的库和转录景观的变化，这些变化提供了对狼疮发病机制中Bleg作用的见解。这些结果可以为Breg靶向治疗和干预的设计提供信息，以恢复自身免疫中的布雷格抑制功能。
B cells can have both pathogenic and protective roles in autoimmune diseases, including systemic lupus erythematosus (SLE). Deficiencies in the number or immunosuppressive function of IL-10 producing regulatory B cells (Bregs) can cause exacerbated autoimmune inflammation. However, the exact role of Bregs in lupus pathogenesis has not been elucidated. We carried out gene expression analysis by scRNA-seq to characterize differences in splenic Breg subsets and molecular profiles through stages of disease progression in lupus-prone mice. Transcriptome-based changes in Bregs from mice with active disease were confirmed by phenotypic analysis. We found that a loss of marginal zone (MZ) lineage Bregs, an increase in plasmablast/plasma cell (PB-PC) lineage Bregs, and overall increases in inflammatory gene signatures were characteristic of active disease as compared to Bregs from the pre-disease stage. However, the frequencies of both MZ Bregs and PB-PCs expressing IL-10 were significantly decreased in active-disease mice. Overall, we have identified changes to the repertoire and transcriptional landscape of Breg subsets associated with active disease that provide insights into the role of Bregs in lupus pathogenesis. These results could inform the design of Breg-targeted therapies and interventions to restore Breg suppressive function in autoimmunity.
影响因子：
7.3
作者：
通讯作者：
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DOI：
10.4049/jimmunol.0902391
发表时间：
2010-05-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
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作者：
Haas KM;Watanabe R;Matsushita T;Nakashima H;Ishiura N;Okochi H;Fujimoto M;Tedder TF
通讯作者：
Tedder TF
DOI：
10.4049/jimmunol.2200098
发表时间：
2022-05-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
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