调节性T细胞在脓毒症中的多方面作用：机制、异质性及病原体针对性疗法

The Multifaceted Role of Regulatory T Cells in Sepsis: Mechanisms, Heterogeneity, and Pathogen-Tailored Therapies.

作者信息

Qin Yingyu, Zhang Jingli

机构信息

Department of Pathogenic Biology and Immunology, Jiangsu Provincial Key Laboratory of Critical Care Medicine, School of Medicine, Southeast University, Nanjing 210096, China.

出版信息

Int J Mol Sci. 2025 Aug 1;26(15):7436. doi: 10.3390/ijms26157436.

DOI:10.3390/ijms26157436

PMID:40806563

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12347338/

Abstract

Sepsis is a life-threatening condition caused by a dysregulated immune response to infection, characterized by an initial hyperinflammatory phase frequently followed by compensatory immunosuppression (CARS). Regulatory T cells (Tregs) play a critical, biphasic role: inadequate suppression during early hyperinflammation fails to control cytokine storms, while excessive/persistent activity in late-phase immunosuppression drives immune paralysis and secondary infection susceptibility. This review explores advances in targeting Treg immunoregulation across bacterial, viral, and fungal sepsis, where pathogenic type critically influenced the types of immunoresponses, shaping Treg heterogeneity in terms of phenotype, survival, and function. Understanding this multifaceted Treg biology offers novel therapeutic avenues, highlighting the need to decipher functional heterogeneity and develop precisely timed, pathogen-tailored immunomodulation to safely harness beneficial Treg roles while mitigating detrimental immunosuppression.

摘要

脓毒症是一种由对感染的免疫反应失调引起的危及生命的病症，其特征是初始的过度炎症期，随后常伴有代偿性免疫抑制（CARS）。调节性T细胞（Tregs）发挥着关键的双相作用：早期过度炎症期间抑制不足无法控制细胞因子风暴，而后期免疫抑制中过度/持续的活性则导致免疫麻痹和继发感染易感性。本综述探讨了针对细菌、病毒和真菌性脓毒症中Treg免疫调节的进展，其中致病类型严重影响免疫反应类型，在表型、存活和功能方面塑造了Treg的异质性。了解这种多方面的Treg生物学提供了新的治疗途径，强调需要破译功能异质性并开发精确计时、针对病原体的免疫调节，以安全地利用有益的Treg作用，同时减轻有害的免疫抑制。