Single-cell transcriptomic analysis uncovers heterogeneity in the labial gland microenvironment of primary Sjögren's syndrome

IF 4.7 Q2 IMMUNOLOGY Journal of Translational Autoimmunity Pub Date : 2024-07-16 DOI:10.1016/j.jtauto.2024.100248
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Abstract

Objective

Primary Sjögren's syndrome (pSS) is a systemic autoimmune disorder with an unclear pathogenetic mechanism in the labial gland. This study aims to investigate the cellular and molecular mechanisms contributing to the development of this disease.

Methods

Single-cell RNA sequencing (scRNA-seq) was performed on 32,337 cells of labial glands from three pSS patients and three healthy individuals. We analyzed all cell subsets implicated in pSS pathogenesis.

Results

Our research revealed diminished differentiation among epithelial cells, concomitant with an enhancement of interferons (IFNs)-mediated signaling pathways. This indicates a cellular functional shift in reaction to inflammatory triggers. Moreover, we observed an augmentation in the population of myofibroblasts and endothelial cells, likely due to the intensified IFNs signaling, suggesting a possible reconfiguration of tissue structure and vascular networks in the impacted regions. Within the immune landscape, there was an apparent increase in immunosuppressive macrophages and dendritic cells (DCs), pointing to an adaptive immune mechanism aimed at modulating inflammation and averting excessive tissue harm. Elevated activation levels of CD4+T cells, along with a rise in regulatory T (Treg) cells, were noted, indicating a nuanced immune interplay designed to manage the inflammatory response. In the CD8+T cell subsests, we detected a notable increase in cells expressing granzyme K (GZMK), signaling an intensified cytotoxic activity. Additionally, the escalated presence of T cells with high levels of heat shock proteins (HSPs) suggests a cellular stress condition, possibly associated with persistent low-grade inflammation, mirroring the chronic aspect of the condition.

Conclusions

Our research identified distinct stromal and immune cell populations linked to pSS, revealing new potential targets for its management. The activation of myeloid, B, and T cells could contribute to pSS pathogenesis, providing important guidance for therapeutic approaches.

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单细胞转录组分析揭示原发性斯约格伦综合征唇腺微环境的异质性
目的原发性斯约格伦综合征(pSS)是一种全身性自身免疫性疾病,唇腺的发病机制尚不清楚。本研究旨在探讨导致这种疾病发生的细胞和分子机制。方法对来自三名 pSS 患者和三名健康人的 32,337 个唇腺细胞进行了单细胞 RNA 测序(scRNA-seq)。我们分析了与 pSS 发病机制有关的所有细胞亚群。结果我们的研究发现,上皮细胞分化减弱,同时干扰素(IFNs)介导的信号通路增强。这表明细胞对炎症诱因的反应发生了功能性转变。此外,我们还观察到肌成纤维细胞和内皮细胞的数量增加,这可能是由于 IFNs 信号的增强,表明受影响区域的组织结构和血管网络可能发生了重组。在免疫环境中,免疫抑制巨噬细胞和树突状细胞(DCs)明显增加,这表明适应性免疫机制旨在调节炎症和避免对组织造成过度伤害。CD4+T细胞活化水平升高,调节性T细胞(Treg)增加,这表明免疫系统之间存在着微妙的相互作用,旨在控制炎症反应。在 CD8+T 细胞亚群中,我们检测到表达颗粒酶 K (GZMK) 的细胞明显增加,这表明细胞毒性活性增强。此外,热休克蛋白(HSPs)水平较高的 T 细胞的增加表明细胞处于应激状态,可能与持续的低度炎症有关,反映了病情的慢性方面。结论我们的研究发现了与 pSS 相关的不同基质和免疫细胞群,揭示了治疗 pSS 的新潜在靶点。髓系细胞、B 细胞和 T 细胞的活化可能有助于 pSS 的发病机制,为治疗方法提供了重要指导。
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来源期刊
Journal of Translational Autoimmunity
Journal of Translational Autoimmunity Medicine-Immunology and Allergy
CiteScore
7.80
自引率
2.60%
发文量
33
审稿时长
55 days
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