Department of Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital, Capital Medical University, Beijing, China.
National Center for Respiratory Medicine, Beijing, China.
Front Immunol. 2022 Feb 17;13:804034. doi: 10.3389/fimmu.2022.804034. eCollection 2022.
Interstitial lung diseases (ILDs) secondary to anti-synthetase syndrome (ASS) greatly influence the prognoses of patients with ASS. Here we aimed to investigate the peripheral immune responses to understand the pathogenesis of this condition.
We performed single-cell RNA sequencing (scRNA-seq) of peripheral blood mononuclear cells (PBMCs) from 5 patients with ASS-ILD and 3 healthy donors (HDs). Flow cytometry of PBMCs was performed to replenish the results of scRNA-seq.
We used scRNA-seq to depict a high-resolution visualization of cellular landscape in PBMCs from patients with ASS-ILD. Patients showed upregulated interferon responses among NK cells, monocytes, T cells, and B cells. And the ratio of effector memory CD8 T cells to naïve CD8 T cells was significantly higher in patients than that in HDs. Additionally, Th1, Th2, and Th17 cell differentiation signaling pathways were enriched in T cells. Flow cytometry analyses showed increased proportions of Th17 cells and Th2 cells, and decreased proportion of Th1 cells in patients with ASS-ILD when compared with HDs, evaluated by the expression patterns of chemokine receptors.
The scRNA-seq data analyses reveal that ASS-ILD is characterized by upregulated interferon responses, altered CD8 T cell homeostasis, and involvement of differentiation signaling pathways of CD4 T cells. The flow cytometry analyses show that the proportions of Th17 cells and Th2 cells are increased and the proportion of Th1 cells is decreased in patients with ASS-ILD. These findings may provide foundations of novel therapeutic targets for patients with this condition.
抗合成酶综合征（ASS）相关的间质性肺病（ILDs）极大地影响了 ASS 患者的预后。在此，我们旨在研究外周免疫反应，以了解该疾病的发病机制。
我们对 5 例 ASS-ILD 患者和 3 名健康供体（HDs）的外周血单个核细胞（PBMCs）进行了单细胞 RNA 测序（scRNA-seq）。通过 PBMCs 的流式细胞术补充 scRNA-seq 的结果。
我们使用 scRNA-seq 描绘了 ASS-ILD 患者 PBMCs 中细胞景观的高分辨率可视化。患者的 NK 细胞、单核细胞、T 细胞和 B 细胞中存在干扰素反应上调。与 HDs 相比，患者的效应记忆 CD8 T 细胞与初始 CD8 T 细胞的比例显著更高。此外，T 细胞中富集了 Th1、Th2 和 Th17 细胞分化信号通路。流式细胞术分析显示，与 HDs 相比，ASS-ILD 患者的 Th17 细胞和 Th2 细胞比例增加，Th1 细胞比例降低，通过趋化因子受体的表达模式进行评估。
scRNA-seq 数据分析表明，ASS-ILD 的特征是干扰素反应上调、CD8 T 细胞稳态改变以及 CD4 T 细胞分化信号通路的参与。流式细胞术分析显示，ASS-ILD 患者的 Th17 细胞和 Th2 细胞比例增加，Th1 细胞比例降低。这些发现可能为该疾病患者提供新的治疗靶点的基础。
