CD38/p53/ME1 axis promotes T cell senescence during HIV infection via suppression of mitochondrial function
10.3760/cma.j.cn112309-20250205-00029
- VernacularTitle:CD38/p53/ME1轴通过抑制线粒体功能促进HIV感染中的T细胞衰老
- Author:
Xin ZHONG
1
;
Chengbo SONG
1
;
Dingning LIU
1
;
Mei LIU
1
;
Yajing FU
1
;
Yongjun JIANG
1
;
Haibo DING
1
;
Zining ZHANG
1
Author Information
1. 中国医科大学附属第一医院，传染病诊治国家重点实验室，国家卫生健康委员会艾滋病防治重点实验室，国家临床检验医学研究中心，沈阳 110001
- Publication Type:Journal Article
- Keywords:
Human immunodeficiency virus;
CD38;
Malic enzyme 1;
T cells;
Mitochondria;
Immune senescence
- From:
Chinese Journal of Microbiology and Immunology
2025;45(4):269-276
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the role of the CD38/p53/ME1 axis in regulating T cell mitochondrial function and senescence during HIV infection.Methods:The expression of CD38 on T cells was examined in HIV-infected individuals receiving antiretroviral therapy(ART), untreated HIV-infected individuals, and HIV-negative healthy controls. Flow cytometry was used to compare senescence markers and mitochondrial function between CD38 + and CD38 - T cells. Malic enzyme 1(ME1) mRNA levels were measured by qRT-PCR in T cells treated with the CD38 inhibitor 78c. Mitochondrial function and senescence were assessed in T cells treated with an ME1 inhibitor. The regulatory mechanism of CD38-mediated ME1 downregulation was further explored. Results:Compared to healthy controls, T cells from HIV-infected individuals exhibited significantly elevated CD38 expression, which persisted despite ART. CD38 + T cells showed increased senescence (CD28 -CD57 + subset) and mitochondrial dysfunction[depolarization and reactive oxygen species(ROS) accumulation]. CD38 inhibition upregulated ME1 mRNA level ( P<0.05). ME1 suppression led to mitochondrial impairment (reduced membrane potential and elevated ROS) and senescence in T cells. Mechanistically, CD38 depletion increased NAD + levels and SIRT1 activity, while SIRT1/p53 inhibition rescued ME1 expression, suggesting CD38 regulates ME1 via the NAD + /SIRT1/p53 axis. Conclusions:The CD38/p53/ME1 axis drives T cell senescence in HIV infection by disrupting mitochondrial function. Targeting this pathway may ameliorate CD38-associated T cell dysfunction and immune aging.
