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在自身免疫中,具有 B 细胞促进功能的与年龄相关的 CD4 T 细胞受 ZEB2 调控。

Age-associated CD4 T cells with B cell-promoting functions are regulated by ZEB2 in autoimmunity.

机构信息

Department of Allergy and Rheumatology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.

Department of Functional Genomics and Immunological Diseases, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.

出版信息

Sci Immunol. 2024 Mar 29;9(93):eadk1643. doi: 10.1126/sciimmunol.adk1643.

Abstract

Aging is a significant risk factor for autoimmunity, and many autoimmune diseases tend to onset during adulthood. We conducted an extensive analysis of CD4 T cell subsets from 354 patients with autoimmune disease and healthy controls via flow cytometry and bulk RNA sequencing. As a result, we identified a distinct CXCR3CD4 effector memory T cell subset that expands with age, which we designated "age-associated T helper (TA) cells." TA cells exhibited both a cytotoxic phenotype and B cell helper functions, and these features were regulated by the transcription factor ZEB2. Consistent with the highly skewed T cell receptor usage of TA cells, gene expression in TA cells from patients with systemic lupus erythematosus reflected disease activity and was affected by treatment with a calcineurin inhibitor. Moreover, analysis of single-cell RNA sequencing data revealed that TA cells infiltrate damaged organs in patients with autoimmune diseases. Together, our characterization of TA cells may facilitate improved understanding of the relationship between aging and autoimmune diseases.

摘要

衰老是自身免疫的一个重要危险因素,许多自身免疫性疾病往往在成年期发病。我们通过流式细胞术和批量 RNA 测序对 354 名自身免疫性疾病患者和健康对照者的 CD4 T 细胞亚群进行了广泛分析。结果,我们鉴定出一种独特的 CXCR3CD4 效应记忆 T 细胞亚群随年龄增长而扩增,我们将其命名为“与年龄相关的辅助性 T 细胞(TA 细胞)”。TA 细胞表现出细胞毒性表型和 B 细胞辅助功能,这些特征受转录因子 ZEB2 调控。与 TA 细胞高度偏倚的 T 细胞受体使用一致,红斑狼疮患者 TA 细胞中的基因表达反映了疾病活动,并受钙调神经磷酸酶抑制剂治疗的影响。此外,单细胞 RNA 测序数据的分析表明,TA 细胞浸润自身免疫性疾病患者受损的器官。总之,我们对 TA 细胞的特征描述可能有助于更好地理解衰老与自身免疫性疾病之间的关系。

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