Fouka Evangelia, Lindén Anders, Bossios Apostolos
Division for Lung and Airway Research, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Lung Laboratory, Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden.
Front Immunol. 2025 Jun 16;16:1598257. doi: 10.3389/fimmu.2025.1598257. eCollection 2025.
Bronchiectasis is a chronic airway disease characterized by dysbiosis, persistent inflammation, and permanent structural airway damage. Neutrophilic inflammation is a key pathogenic feature, as indicated by enhanced neutrophil-derived proteases and formation of neutrophil extracellular traps (NETs), associated with poor prognosis. However, recent studies have identified an eosinophilic endotype in up to 30% of patients, characterized by higher levels of type 2 (T2) cytokines and fractional exhaled nitric oxide (FeNO). The role of T helper (Th) cells in the dysregulated inflammatory environment of bronchiectasis remains unclear. Evidence suggests that persistent bacterial infection can skew adaptive immunity from Th1 toward Th2 response, while the airway microbiome-IL-17 axis is also a critical regulator of chronic inflammation. T regulatory (Treg) cells have been shown to play a protective role against excessive chronic inflammation by modulating the function of several types of effector cells, including the Th17 subset. However, the capacity of this subset to delay or prevent disease progression remains to be determined Microbial dysbiosis, with loss of diversity and increased quantity of bacterial pathogens, may also be important for disease progression, and emerging evidence indicates that distinct inflammatory endotypes associate with specific microbiota alterations, especially in severe disease. In this review, we provide an overview of the immune cells and cytokine signaling that are involved in the pathogenesis of bronchiectasis. Additionally, we present the main endotypes of bronchiectasis and explore the relationships between the type of inflammation and alterations in microbiota, as well as the potential benefits of targeting specific pathophysiological mechanisms for the management of bronchiectasis. This review also examines how bacterial infection can shift adaptive immunity from Th1 toward Th2 responses, the role of the airway microbiome-IL-17 axis in chronic inflammation and the potential protective role of Treg cells against excessive inflammation. Novel therapeutic strategies are highlighted, with focus on targeting specific cytokine signaling pathways and restoring Th17/Treg balance These developments underscore a shift toward precision medicine in bronchiectasis, emphasizing the importance of identifying specific inflammatory endotypes to tailor treatment strategies effectively.
支气管扩张症是一种慢性气道疾病，其特征为微生物群失调、持续性炎症和气道结构永久性损伤。中性粒细胞炎症是一个关键的致病特征，中性粒细胞衍生蛋白酶的增加和中性粒细胞胞外诱捕网（NETs）的形成表明了这一点，这与预后不良相关。然而，最近的研究发现，高达30%的患者存在嗜酸性粒细胞亚型，其特征是2型（T2）细胞因子和呼出一氧化氮分数（FeNO）水平较高。辅助性T（Th）细胞在支气管扩张症失调的炎症环境中的作用仍不清楚。有证据表明，持续性细菌感染可使适应性免疫从Th1反应偏向Th2反应，而气道微生物群-白细胞介素-17轴也是慢性炎症的关键调节因子。调节性T（Treg）细胞已被证明可通过调节包括Th17亚群在内的几种效应细胞的功能，对过度的慢性炎症起到保护作用。然而，该亚群延缓或预防疾病进展的能力仍有待确定。微生物群失调，伴随着细菌病原体多样性的丧失和数量的增加，可能对疾病进展也很重要，新出现的证据表明，不同的炎症亚型与特定的微生物群改变有关，尤其是在严重疾病中。在这篇综述中，我们概述了参与支气管扩张症发病机制的免疫细胞和细胞因子信号传导。此外，我们介绍了支气管扩张症的主要亚型，探讨了炎症类型与微生物群改变之间的关系，以及针对特定病理生理机制治疗支气管扩张症的潜在益处。这篇综述还研究了细菌感染如何使适应性免疫从Th1反应转向Th2反应、气道微生物群-白细胞介素-17轴在慢性炎症中的作用以及Treg细胞对过度炎症的潜在保护作用。强调了新的治疗策略，重点是针对特定的细胞因子信号通路和恢复Th17/Treg平衡。这些进展凸显了支气管扩张症向精准医学的转变，强调了识别特定炎症亚型以有效定制治疗策略的重要性。
