Novel insights into the heterogeneity of FOXP3 + Treg cells in drug-induced allergic reactions through single-cell transcriptomics.

IF 3.3 4区 医学 Q3 IMMUNOLOGY
Immunologic Research Pub Date : 2024-10-01 Epub Date: 2024-07-29 DOI:10.1007/s12026-024-09509-1
Wei Shen, Yibo Liang, Dong Lv, Nan Xie
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引用次数: 0

Abstract

This study uncovers the novel heterogeneity of FOXP3 + regulatory T (Treg) cells and their pivotal role in modulating immune responses during drug-induced allergic reactions, employing cutting-edge single-cell transcriptomics. We established a mouse model for drug-induced allergic reactions and utilized single-cell RNA sequencing (scRNA-seq) to analyze the transcriptomic landscapes of FOXP3 + Treg cells isolated from affected tissues. The study involved both in vitro and in vivo approaches to evaluate the impact of FOXP3 expression levels on the immunoregulatory functions of Treg cells during allergic responses. Techniques included flow cytometry, cluster analysis, principal component analysis (PCA), CCK8 and CSFE assays for cell proliferation, LDH release assays for toxicity, ELISA for cytokine profiling, and CRISPR/Cas9 technology for gene editing. Our findings revealed significant transcriptomic heterogeneity among FOXP3 + Treg cells in the context of drug-induced allergic reactions, with distinct subpopulations exhibiting unique gene expression profiles. This heterogeneity suggests specialized roles in immune regulation. We observed a decrease in the proliferative capacity and cytokine secretion of FOXP3 + Treg cells following allergic stimulation, alongside an increase in reaction toxicity. Manipulating FOXP3 expression levels directly influenced these outcomes, where FOXP3 deletion exacerbated allergic responses, whereas its overexpression mitigated them. Notably, in vivo experiments demonstrated that FOXP3 overexpression significantly reduced the severity of allergic skin reactions in mice. Our study presents novel insights into the heterogeneity and crucial immunoregulatory role of FOXP3 + Treg cells during drug-induced allergic reactions. Overexpression of FOXP3 emerges as a potential therapeutic strategy to alleviate such allergic responses. These findings contribute significantly to our understanding of immune regulation and the development of targeted treatments for drug-induced allergies.

Abstract Image

通过单细胞转录组学深入了解药物诱导过敏反应中 FOXP3 + Treg 细胞的异质性。
本研究利用最前沿的单细胞转录组学揭示了 FOXP3 + 调节性 T(Treg)细胞的新型异质性及其在药物诱导的过敏反应中调节免疫反应的关键作用。我们建立了一个药物诱导过敏反应的小鼠模型,并利用单细胞 RNA 测序(scRNA-seq)分析了从受影响组织中分离出来的 FOXP3 + Treg 细胞的转录组图谱。该研究采用体外和体内方法评估过敏反应期间 FOXP3 表达水平对 Treg 细胞免疫调节功能的影响。采用的技术包括流式细胞术、聚类分析、主成分分析(PCA)、细胞增殖的 CCK8 和 CSFE 检测、毒性的 LDH 释放检测、细胞因子分析的 ELISA 以及基因编辑的 CRISPR/Cas9 技术。我们的研究结果表明,在药物诱导的过敏反应中,FOXP3 + Treg 细胞之间存在明显的转录组异质性,不同的亚群表现出独特的基因表达谱。这种异质性表明它们在免疫调节中发挥着特殊的作用。我们观察到过敏刺激后 FOXP3 + Treg 细胞的增殖能力和细胞因子分泌减少,同时反应毒性增加。操纵 FOXP3 的表达水平会直接影响这些结果,其中 FOXP3 的缺失会加剧过敏反应,而过表达则会减轻过敏反应。值得注意的是,体内实验表明,过表达 FOXP3 能显著减轻小鼠皮肤过敏反应的严重程度。我们的研究对药物诱导过敏反应过程中 FOXP3 + Treg 细胞的异质性和关键免疫调节作用提出了新的见解。过表达 FOXP3 是缓解此类过敏反应的一种潜在治疗策略。这些发现极大地促进了我们对免疫调节的理解以及药物诱发过敏的靶向治疗方法的开发。
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来源期刊
Immunologic Research
Immunologic Research 医学-免疫学
CiteScore
6.90
自引率
0.00%
发文量
83
审稿时长
6-12 weeks
期刊介绍: IMMUNOLOGIC RESEARCH represents a unique medium for the presentation, interpretation, and clarification of complex scientific data. Information is presented in the form of interpretive synthesis reviews, original research articles, symposia, editorials, and theoretical essays. The scope of coverage extends to cellular immunology, immunogenetics, molecular and structural immunology, immunoregulation and autoimmunity, immunopathology, tumor immunology, host defense and microbial immunity, including viral immunology, immunohematology, mucosal immunity, complement, transplantation immunology, clinical immunology, neuroimmunology, immunoendocrinology, immunotoxicology, translational immunology, and history of immunology.
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