1型糖尿病中鞘氨醇-1-磷酸及其受体的改变：一项综合临床和单细胞转录组研究
Alterations of sphingosine-1-phosphate and its receptors in type 1 diabetes mellitus: an integrated clinical and single-cell transcriptomic study.
摘要(中文译文)
1型糖尿病（T1DM）是一种T细胞介导的自身免疫性疾病。鞘氨醇-1-磷酸（S1P）信号通路调控淋巴细胞运输，但其在T1DM中的状态尚缺乏充分表征。本研究通过整合单细胞转录组学和临床分析，探讨了T1DM中S1P及鞘氨醇-1-磷酸受体1（S1PR1）的变化。我们对T1DM患者和健康对照者的结肠组织进行了单细胞RNA测序（scRNA-seq），并辅以非肥胖糖尿病（NOD）小鼠在糖尿病前期（4周）和疾病期（12周）的分析。定量检测了血清总S1P、高密度脂蛋白结合型S1P（HDL-S1P）及载脂蛋白M（ApoM），并进一步对肠道T细胞亚群进行了转录组功能富集分析。scRNA-seq显示T1DM患者与健康对照者肠道免疫细胞中S1P受体表达存在差异。T1DM患者T细胞亚群中S1PR1表达降低，尤其是CD8+效应T细胞。在NOD小鼠中，S1PR1表达在4周时呈聚集模式，至12周时更为弥散且淋巴细胞中水平降低。临床上，T1DM患者血清总S1P显著升高，且独立增加T1DM风险，而HDL-S1P降低，ApoM水平不变。血清S1P与糖化血红蛋白（HbA1c）和白细胞介素-6（IL-6）呈正相关，与低血糖事件呈负相关。转录组富集分析提示肠道CD8效应T细胞和调节性T细胞发生功能重编程。T1DM与S1P-S1PR1通路改变相关，其特征为肠道S1PR1表达降低、循环总S1P升高以及功能性HDL-S1P降低（尽管ApoM稳定）。S1P与T1DM状态独立相关，并与血糖控制和炎症相关，提示其作为疾病相关生物标志物的潜力。
Abstract
Type 1 diabetes (T1DM) is a T cell-mediated autoimmune disease. The sphingosine-1-phosphate (S1P) signaling pathway regulates lymphocyte trafficking, but its status in T1DM remains poorly characterized. This study investigated S1P and sphingosine-1-phosphate receptor 1(S1PR1) alterations in T1DM through integrated single-cell transcriptomic and clinical analysis. We performed single-cell RNA sequencing (scRNA-seq)on colonic tissues from T1DM patients and healthy controls, complemented by analysis in non-obese diabetic (NOD) mice at pre-diabetic (4 weeks) and disease stages (12 weeks).Serum total S1P, HDL-bound S1P, and apolipoprotein M (ApoM) were quantified, and transcriptomic functional enrichment of intestinal T cell subsets was further performed. scRNA-seq showed differences in S1P receptor expression in intestinal immune cells between T1DM patients and healthy controls. S1PR1 expression was lower in T cell subsets, particularly CD8+ effector T cells, in T1DM patients. In NOD mice, S1PR1 expression showed a clustered pattern at 4 weeks and was more diffuse with lower levels in lymphocytes at 12 weeks. Clinically, serum total S1P was significantly elevated in T1DM and independently increased T1DM risk, while high-density lipoprotein-bound (HDL-bound) sphingosine-1-phosphate (HDL-S1P) was decreased with unchanged apolipoprotein M (ApoM) levels. Serum S1P positively correlated with glycated hemoglobin (HbA1c) and interleukin-6 (IL-6), and was inversely associated with hypoglycemic episodes. Transcriptomic enrichment indicated functional reprogramming of intestinal CD8 effector T and regulatory T cells. T1DM is associated with alterations in the S1P-S1PR1 pathway, characterized by reduced intestinal S1PR1 expression, elevated circulating total S1P, and decreased functional HDL-bound S1P despite stable ApoM.S1P is independently associated with T1DM status and correlates with glycemic control and inflammation, suggesting its potential as a disease-related biomarker.
如何引用
AMA
Dongyan Chen, Fuhua Zhang, Tian Ren, Haiyan Chi, Mengyang Shen, Shiyu Kang, et al. Alterations of sphingosine-1-phosphate and its receptors in type 1 diabetes mellitus: an integrated clinical and single-cell transcriptomic study.. Frontiers in immunology. 2026; doi:10.3389/fimmu.2026.1838952.
APA
Dongyan Chen, Fuhua Zhang, Tian Ren, Haiyan Chi, Mengyang Shen, Shiyu Kang, et al (2026). Alterations of sphingosine-1-phosphate and its receptors in type 1 diabetes mellitus: an integrated clinical and single-cell transcriptomic study.. Frontiers in immunology. https://doi.org/10.3389/fimmu.2026.1838952
GB/T 7714
Dongyan Chen, Fuhua Zhang, Tian Ren, Haiyan Chi, Mengyang Shen, Shiyu Kang, et al. Alterations of sphingosine-1-phosphate and its receptors in type 1 diabetes mellitus: an integrated clinical and single-cell transcriptomic study.[J]. Frontiers in immunology, 2026 doi:10.3389/fimmu.2026.1838952.
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