Chronic rhinosinusitis with nasal polyps (CRSwNP) is a subtype of chronic rhinosinusitis (CRS) characterized by the presence of nasal polyps (NP) in the paranasal mucosa. Despite the complex etiology, NP is believed to result from chronic inflammation. The long-term aftermath of the type 2 response is responsible for symptoms seen in NP patients, i.e. rhinorrhea, hyposmia, and nasal obstruction. Immune cellular tolerogenic mechanisms, particularly CD4 + Foxp3 + regulatory T cells (Tregs), are crucial to curtail inflammatory responses. Current evidence suggests impaired Treg activity is the main reason underlying the compromise of self-tolerance, contributing to the onset of CRSwNP. There is compelling evidence that tumor necrosis factor 2 (TNFR2) is preferentially expressed by Tregs, and TNFR2 is able to identify the most potent suppressive subset of Tregs. Tumor necrosis factor (TNF)-TNFR2 interaction plays a decisive role in the activation and expansion of Tregs. This review summarizes current understanding of Tregs biology, focusing on the discussion of the recent advances in the study of TNF-TNFR2 axis in the upregulation of Treg function as a negative feedback mechanism in the control of chronic inflammation. The role of dysregulation of Tregs in the immunopathogenesis of CRSwNP will be analyzed. The future perspective on the harnessing Tregs-mediated self-tolerant mechanism in the management of CRSwNP will be introduced.

中文翻译：

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CD4+ Foxp3+ 调节性 T 细胞在调节慢性鼻窦炎伴鼻息肉炎症微环境中的作用：进展与未来展望

慢性鼻窦炎伴鼻息肉（CRSwNP）是慢性鼻窦炎（CRS）的一种亚型，其特征是鼻旁粘膜存在鼻息肉（NP）。尽管病因复杂，但 NP 被认为是由慢性炎症引起的。 2 型反应的长期后果是 NP 患者出现症状的原因，即鼻漏、嗅觉减退和鼻塞。免疫细胞耐受机制，特别是 CD4 + Foxp3 + 调节性 T 细胞 (Treg)，对于抑制炎症反应至关重要。目前的证据表明，Treg 活性受损是自我耐受性受损的主要原因，从而导致 CRSwNP 的发生。有令人信服的证据表明肿瘤坏死因子 2 (TNFR2) 优先由 Tregs 表达，并且 TNFR2 能够识别最有效的抑制性 Tregs 子集。肿瘤坏死因子(TNF)-TNFR2相互作用在Tregs的激活和扩增中起决定性作用。本文综述了目前对Tregs生物学的认识，重点讨论了TNF-TNFR2轴上调Treg功能作为控制慢性炎症的负反馈机制的研究最新进展。将分析 Tregs 失调在 CRSwNP 免疫发病机制中的作用。将介绍利用 Tregs 介导的自我耐受机制治疗 CRSwNP 的未来前景。