关键词: CD8+ T cell immune checkpoint lymphocyte activation gene 3 mycobacterium tuberculosis tuberculosis

Mesh : Lymphocyte Activation Gene 3 Protein Humans Mycobacterium tuberculosis / immunology genetics CD8-Positive T-Lymphocytes / immunology Tuberculosis / immunology microbiology Animals Antigens, CD / genetics BCG Vaccine / immunology Macrophages / immunology microbiology Interleukin-2 / metabolism genetics Gene Expression Profiling Tuberculosis, Pulmonary / immunology microbiology Interleukin-12 / genetics metabolism Perforin / genetics metabolism Male

来  源:   DOI:10.3389/fcimb.2024.1410015   PDF(Pubmed)

Abstract:
UNASSIGNED: Tuberculosis (TB) persists as a global health challenge, with its treatment hampered by the side effects of long-term combination drug therapies and the growing issue of drug resistance. Therefore, the development of novel therapeutic strategies is critical. This study focuses on the role of immune checkpoint molecules (ICs) and functions of CD8+ T cells in the search for new potential targets against TB.
UNASSIGNED: We conducted differential expression genes analysis and CD8+ T cell functional gene analysis on 92 TB samples and 61 healthy individual (HI) samples from TB database GSE83456, which contains data on 34,603 genes. The GSE54992 dataset was used to validated the findings. Additionally, a cluster analysis on single-cell data from primates infected with mycobacterium tuberculosis and those vaccinated with BCG was performed.
UNASSIGNED: The overexpression of LAG-3 gene was found as a potentially important characteristic of both pulmonary TB (PTB) and extrapulmonary TB (EPTB). Further correlation analysis showed that LAG-3 gene was correlated with GZMB, perforin, IL-2 and IL-12. A significant temporal and spatial variation in LAG-3 expression was observed in T cells and macrophages during TB infection and after BCG vaccination.
UNASSIGNED: LAG-3 was overexpressed in TB samples. Targeting LAG-3 may represent a potential therapeutic target for tuberculosis.
摘要:
结核病(TB)仍然是全球健康挑战,长期联合药物治疗的副作用和日益严重的耐药性问题阻碍了其治疗。因此,开发新的治疗策略至关重要。这项研究的重点是免疫检查点分子(IC)的作用和CD8+T细胞的功能在寻找新的潜在目标的结核病。
我们对来自TB数据库GSE83456的92个TB样本和61个健康个体(HI)样本进行了差异表达基因分析和CD8+T细胞功能基因分析,其中包含34,603个基因的数据。使用GSE54992数据集来验证发现。此外,我们对感染结核分枝杆菌的灵长类动物和接种卡介苗的灵长类动物的单细胞数据进行了聚类分析.
发现LAG-3基因的过表达是肺结核病(PTB)和肺外结核病(EPTB)的潜在重要特征。进一步的相关性分析显示,LAG-3基因与GZMB,穿孔素,IL-2和IL-12。在TB感染期间和BCG疫苗接种后,在T细胞和巨噬细胞中观察到LAG-3表达的显着时间和空间变化。
LAG-3在TB样品中过表达。靶向LAG-3可能代表结核病的潜在治疗靶标。
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