哮喘2型炎症加速CD4<sup>+</sup> T细胞衰老

刘欢; 李泽民; 孙永昌; 阿布都热依木江·艾力; 常春

doi:10.1631/jzus.B2500233

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哮喘2型炎症加速CD4⁺ T细胞衰老

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Research Article | Updated：2026-02-06

哮喘2型炎症加速CD4⁺ T细胞衰老
Type 2 inflammation accelerates CD4⁺ T-cell senescence in asthma
浙江大学学报（英文版）（B辑：生物医学和生物技术） 2026年27卷第2期页码：149-163
Affiliations：

1.Department of Respiratory and Critical Care Medicine, Peking University Third Hospital, Beijing 100083, China
2.Research Center for Chronic Airway Diseases, Peking University Health Science Center, Beijing 100083, China
3.Department of Medical Oncology and Radiation Sickness, Peking University Third Hospital, Beijing 100083, China
Funds：

the National Natural Science Foundation of China(82370032;82170028;81902909);the Beijing Natural Science Foundation(7232205);the Zhong Nanshan Medical Foundation of Guangdong Province(ZNSXS-20240004);the Peking University Third Hospital’s Cohort Construction Project(BYSYDL2021020);the Key Clinical Projects of the Peking University Third Hospital(BYSYZD2023009)
DOI：10.1631/jzus.B2500233
中图分类号：
CSTR：
收稿：2025-05-06，

修回：2025-08-13，

纸质出版：2026-02-06
Accepted：

刘欢,李泽民,孙永昌等.哮喘2型炎症加速CD4⁺ T细胞衰老[J].浙江大学学报（英文版）（B辑：生物医学和生物技术）,2026,27(02):149-163.

Huan LIU, Zemin LI, Yongchang SUN, et al. Type 2 inflammation accelerates CD4⁺ T-cell senescence in asthma[J]. Journal of Zhejiang University-SCIENCE B, 2026, 27(2): 149-163.
刘欢,李泽民,孙永昌等.哮喘2型炎症加速CD4⁺ T细胞衰老[J].浙江大学学报（英文版）（B辑：生物医学和生物技术）,2026,27(02):149-163. DOI： 10.1631/jzus.B2500233.

Huan LIU, Zemin LI, Yongchang SUN, et al. Type 2 inflammation accelerates CD4⁺ T-cell senescence in asthma[J]. Journal of Zhejiang University-SCIENCE B, 2026, 27(2): 149-163. DOI： 10.1631/jzus.B2500233.

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。

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.

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哮喘2型炎症加速CD4+ T细胞衰老

Type 2 inflammation accelerates CD4+ T-cell senescence in asthma

DOI：10.1631/jzus.B2500233

摘要

Abstract

关键词

Keywords

references

哮喘2型炎症加速CD4⁺ T细胞衰老

Type 2 inflammation accelerates CD4⁺ T-cell senescence in asthma