【摘要】 哮喘是一种复杂的慢性炎症性气道疾病，与免疫细胞异常激活密切相关。T细胞衰老通常伴随免疫功能障碍和持续炎症，但其在哮喘发病中的具体作用尚未明确。本研究发现，哮喘患者中CD4~+衰老T细胞（Tsens）的比例显著高于健康对照，而CD8~+Tsens未出现明显增加。血液和痰液中CD4~+Tsens比例与呼出气一氧化氮（FeNO）、嗜酸性粒细胞数量以及Th2细胞水平呈正相关。在屋尘螨诱导的哮喘小鼠模型中，肺组织内CD4~+Tsens比例同样升高。为干预T细胞衰老，本研究对小鼠进行了包括白细胞介素-4(IL-4)抗体和地塞米松在内的治疗干预，发现IL-4中和可降低哮喘小鼠肺组织CD4~+Tsens比例，并抑制p38丝裂原活化蛋白激酶（MAPK）通路的激活。此外，过继输注衰老CD4~+T细胞到健康小鼠并未引起自发性哮喘，但在屋尘螨诱导的哮喘小鼠中则加重了2型炎症反应。综上所述，本研究揭示了哮喘患者中CD4~+Tsens细胞（CD57~+CD28-）显著增加，并提示2型炎症可驱动CD4~+T细胞衰老，而CD4~+Tsens细胞的过继转移也会加剧哮喘炎症。更多还原

【Abstract】 Asthma is a complex and chronic inflammatory airway disease associated with the abnormal activation of immune cells. T-cell senescence is linked to immune dysfunction and persistent inflammation, but the relationship between asthma and T-cell senescence remains unexplored. This study reveals significantly higher percentages of cluster of differentiation 4-positive(CD4~+) senescent T cells(Tsens) in asthma patients than in healthy controls, while CD8~+ Tsen percentages do not appear to increase. CD4~+ Tsen percentages in both the blood and sputum are positively correlated with fractional exhaled nitric oxide(FeNO) values, eosinophil abundance, and T helper type 2(Th2) cell abundance in the blood. The clinical manifestations of asthma were recreated in a house dust mite(HDM)-induced mouse model. In HDM-exposed mice, CD4~+ Tsen percentages were also elevated in the lungs. To counteract T-cell senescence, therapeutic interventions, including interleukin-4(IL-4) antibodies and dexamethasone, were administered to the mice. IL-4 neutralization reduced CD4~+ Tsen percentages and inhibited p38 mitogen-activated protein kinase(MAPK) activation. Adoptive transfer of CD4~+ Tsens did not induce spontaneous asthma in phosphate-buffered saline(PBS)-treated mice but exacerbated type 2 inflammation in HDM-treated mice. Our study revealed a significant increase in CD4~+ Tsen(CD57~+CD28~-) abundance in asthma patients and suggested that type 2 inflammation drives CD4~+ T-cell senescence in asthma. Furthermore, adoptive transfer of CD4~+ Tsens appears to exacerbate type 2 inflammation.更多还原