CD226 implicated in Akt-dependent apoptosis of CD4 + T cell contributes to asthmatic pathogenesis.

Autor: Zhang Y; Department of Otolaryngology Head and Neck Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.; Department of Immunology, Fourth Military Medical University, Xi'an, Shaanxi, China., Xie Y; Department of Otolaryngology Head and Neck Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China., Zhang X; Department of Immunology, Fourth Military Medical University, Xi'an, Shaanxi, China., Duan C; Department of Immunology, Fourth Military Medical University, Xi'an, Shaanxi, China.; Institute of Medical Research, Northwestern Polytechnical University, Xi'an, Shaanxi, China., Ma J; Department of Immunology, Fourth Military Medical University, Xi'an, Shaanxi, China., Wang Y; Department of Immunology, Fourth Military Medical University, Xi'an, Shaanxi, China., Wu Y; Department of Immunology, Fourth Military Medical University, Xi'an, Shaanxi, China., Shan N; Department of Immunology, Fourth Military Medical University, Xi'an, Shaanxi, China., Cheng K; Department of Immunology, Fourth Military Medical University, Xi'an, Shaanxi, China., Zhuang R; Department of Immunology, Fourth Military Medical University, Xi'an, Shaanxi, China. fmmuzhr@fmmu.edu.cn., Bian K; Department of Otolaryngology Head and Neck Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China. kabian@fmmu.edu.cn.
Jazyk: angličtina
Zdroj: Cell death & disease [Cell Death Dis] 2024 Sep 30; Vol. 15 (9), pp. 705. Date of Electronic Publication: 2024 Sep 30.
DOI: 10.1038/s41419-024-07080-z
Abstrakt: Asthma is a chronic airway inflammatory disease in which CD4 + T cell dysregulation occurs. Here, we investigated the molecular role and clinical significance of CD226, a costimulatory molecule of T lymphocytes, in the development of allergic asthma. Our results revealed that the expression of CD226 was significantly increased in CD4 + effector T cells, especially in T helper (Th) 2 cells and Th17 cells in patients with asthma. Moreover, CD4 + T cell-specific Cd226-knockout mice were generated and together with littermates were challenged with ovalbumin (OVA) to establish a model of allergic asthma. We found that CD226 deficiency in CD4 + T cells mitigated lung inflammation, IgE production, and eosinophil infiltration and reduced airway remodeling in experimental allergic asthma. However, the impact of CD226 on asthma was independent of Treg cell modulation. Through RNA-seq data analysis, the apoptosis pathway was screened. Mechanistically, CD226 deletion promoted CD4 + T cell late apoptosis via the activation of Caspase-3 in an Akt-dependent manner. Furthermore, blocking CD226 signaling with a recombinant fusion protein attenuated asthma features in mice and achieved a good therapeutic effect. Overall, this study revealed a unique role of CD226 in CD4 + T cell regulation in asthma pathogenesis. Therefore, targeting CD226 may provide new insights into the clinical treatment of asthma.
(© 2024. The Author(s).)
Databáze: MEDLINE
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