威尔康奈尔医学院Simone Caielli课题组宣布他们揭示了血液CD4⁺T细胞的单细胞RNA测序分析揭示儿童系统性红斑狼疮中存在不同的辅助性和功能失调调节性T细胞亚群。相关论文于2025年10月21日发表在《自然—免疫学》杂志上。

为揭示系统性红斑狼疮（SLE）患者CD4⁺ T细胞群体的复杂性，研究人员对儿童患者及健康供体的血液分选CD4⁺  T细胞进行了单细胞RNA测序。研究识别出初始T细胞、记忆T细胞、调节性T细胞（T_reg）、增殖性T细胞及干扰素刺激基因高表达（ISG-high）细胞群。在记忆T细胞群体中，滤泡辅助性T细胞和外周辅助性T细胞在狼疮肾炎和/或高疾病活动度患者中显著扩增。细胞毒性特征在重表达CD45RA的效应记忆T细胞（TEMRA）及两个记忆亚群中富集，其中一个亚群与辅助性T10样细胞（TH10）存在重叠。值得注意的是，研究在狼疮肾炎患者中观察到功能失调性T_reg细胞的扩增，同时SLE患者的初始T_reg细胞中TLR5和FCRL3表达上调，提示其可能与黏膜微生物群失调存在潜在关联。这些发现揭示了特定的CD4⁺ T细胞亚群，或可解释SLE中异常的抗体反应及免疫调节功能受损。

附：英文原文

Title: Single-cell RNA profiling of blood CD4+ T cells identifies distinct helper and dysfunctional regulatory clusters in children with SLE

Author: Balasubramanian, Preetha, Balaji, Uthra, Santos, Marina Silva, Baisch, Jeanine, Smitherman, Cynthia, Walters, Lynnette, Sparagana, Paola, Nassi, Lorien, Stewart, Katie, Fuller, Julie, Means, Terry, Savova, Virginia, Banchereau, Jacques F., Wright, Tracey, Pascual, Virginia, Gu, Jinghua, Caielli, Simone

Issue&Volume: 2025-10-21

Abstract: To characterize the complexity of the CD4 T cell compartment in patients with systemic lupus erythematosus (SLE), we performed single-cell RNA sequencing of sorted blood CD4 T cells from pediatric patients and healthy donors. We identified naive, memory, regulatory T (Treg) cell, proliferative and interferon-stimulated gene-high (ISG-high) clusters. Within the memory compartment, both follicular and peripheral helper cells were expanded in patients with lupus nephritis and/or high disease activity. Cytotoxic signatures were enriched in effector memory T cells re-expressing CD45RA (TEMRA), as well as in two memory subclusters, one of which overlapped with T helper 10-like cells (TH10). Notably, we observed an expansion of dysfunctional Treg cells in patients with lupus nephritis, along with upregulation of TLR5 and FCRL3 in SLE-naive Treg cells, suggesting a potential link with mucosal microbial dysbiosis. These findings highlight distinct CD4 T cell subsets that may contribute to aberrant antibody responses and impaired immune regulation in SLE.

DOI: 10.1038/s41590-025-02297-2

Source: https://www.nature.com/articles/s41590-025-02297-2