Huang Jun, Tang Jia, Zhang Chen, Liu Tingting, Deng Zhiyong, Liu Lei
Department of Rheumatology and Immunology, The First People's Hospital of Kunshan, Jiangsu, Suzhou, 215300, China.
J Transl Autoimmun. 2024 Jul 16;9:100248. doi: 10.1016/j.jtauto.2024.100248. eCollection 2024 Dec.
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.
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.
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 CD4T 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 CD8T 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.
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.
原发性干燥综合征（pSS）是一种系统性自身免疫性疾病，其唇腺发病机制尚不清楚。本研究旨在探讨导致该疾病发生发展的细胞和分子机制。
对3例pSS患者和3例健康个体的唇腺32337个细胞进行单细胞RNA测序（scRNA-seq）。我们分析了所有与pSS发病机制相关的细胞亚群。
我们的研究发现上皮细胞分化减少，同时干扰素（IFN）介导的信号通路增强。这表明细胞功能在对炎症触发因素的反应中发生了转变。此外，我们观察到肌成纤维细胞和内皮细胞数量增加，可能是由于IFN信号增强，提示受影响区域的组织结构和血管网络可能发生了重新配置。在免疫格局中，免疫抑制性巨噬细胞和树突状细胞（DC）明显增加，表明存在一种旨在调节炎症和避免过度组织损伤的适应性免疫机制。注意到CD4T细胞的激活水平升高，以及调节性T（Treg）细胞数量增加，表明存在一种微妙的免疫相互作用以控制炎症反应。在CD8T细胞亚群中，我们检测到表达颗粒酶K（GZMK）的细胞显著增加，表明细胞毒性活性增强。此外，高水平热休克蛋白（HSP）的T细胞数量增加表明存在细胞应激状态，可能与持续性低度炎症有关，反映了该疾病的慢性特征。
我们的研究确定了与pSS相关的不同基质和免疫细胞群，揭示了其治疗的新潜在靶点。髓样细胞、B细胞和T细胞的激活可能促成pSS的发病机制，为治疗方法提供了重要指导。
