Zhao Chenyi, Song Xuefei, Yang Dan, Lv Chenbing, Li Yuhan, Abdalla Abualgasim Elgaili, Shi Tingyu, Wang Guirong, Xie Longxiang
School of Basic Medical Sciences, Henan University, Kaifeng 475004 Henan, China.
Inner Mongolia Fourth Hospital, Hohhot, Inner Mongolia Autonomous Region 010000, China.
J Genet Eng Biotechnol. 2025 Sep;23(3):100537. doi: 10.1016/j.jgeb.2025.100537. Epub 2025 Jul 21.
Immune cells and plasma metabolites may play important roles in the development of pulmonary diseases, but the relationship between different immune cells, plasma metabolites and various pulmonary diseases is still unclear. In this study, we aim to employ Mendelian randomization (MR) to investigate the causality between immune cells, pulmonary diseases and plasma metabolites.
We analyzed immune cells and seven pulmonary diseases, including interstitial lung disease (ILD), idiopathic pulmonary fibrosis (IPF), lung cancer, pneumonia, chronic obstructive pulmonary disease (COPD), sleep apnea syndrome (SAS), and tuberculosis (TB), using genome-wide association analysis (GWAS) data for immune cells as an exposure factor and seven lung diseases as outcomes. Plasma metabolites GWAS data served as mediators. We applied MR analysis to explore the relationship between immune cells and pulmonary diseases, followed by two-step mediation analysis to identify potential metabolites that may mediate this association.
As shown in the results, immune cells contribute to disease progression by reducing the protective effect of metabolites on disease or enhancing the promoting effect of metabolites on disease. These include CD4/CD8br and lung cancer, CD62L-CD86+ myeloid DC AC and Pneumonia, and Naive DN (CD4-CD8-) %T cell and COPD. On the other hand, immune cells suppress disease by increasing the inhibitory effect of metabolites on disease or decreasing the promoting effect of metabolites on disease, These include CD39 on CD39+ CD8br and ILD, CD28+ CD45RA+ CD8br AC and TB, Activated & secreting Treg AC and SAS, HLA DR on DC and IPF.
We clarify the importance of the potential mechanisms pertaining to immune cells, metabolites, and pulmonary diseases, highlighting the complex interactions among these factors. This understanding may assist in the diagnosis and treatment of patients with pulmonary diseases.
免疫细胞和血浆代谢物可能在肺部疾病的发展中发挥重要作用，但不同免疫细胞、血浆代谢物与各种肺部疾病之间的关系仍不清楚。在本研究中，我们旨在采用孟德尔随机化（MR）方法来研究免疫细胞、肺部疾病和血浆代谢物之间的因果关系。
我们使用免疫细胞的全基因组关联分析（GWAS）数据作为暴露因素，七种肺部疾病作为结局，分析了免疫细胞与七种肺部疾病，包括间质性肺疾病（ILD）、特发性肺纤维化（IPF）、肺癌、肺炎、慢性阻塞性肺疾病（COPD）、睡眠呼吸暂停综合征（SAS）和肺结核（TB）。血浆代谢物GWAS数据作为中介变量。我们应用MR分析来探索免疫细胞与肺部疾病之间的关系，随后进行两步中介分析以确定可能介导这种关联的潜在代谢物。
结果显示，免疫细胞通过降低代谢物对疾病的保护作用或增强代谢物对疾病的促进作用来促进疾病进展。这些包括CD4/CD8br与肺癌、CD62L - CD86 + 髓样DC AC与肺炎、幼稚DN（CD4 - CD8 - ）%T细胞与COPD。另一方面，免疫细胞通过增加代谢物对疾病的抑制作用或降低代谢物对疾病的促进作用来抑制疾病，这些包括CD39 + CD8br上的CD39与ILD、CD28 + CD45RA + CD8br AC与TB、活化并分泌的Treg AC与SAS、DC上的HLA DR与IPF。
我们阐明了免疫细胞、代谢物和肺部疾病潜在机制的重要性，突出了这些因素之间的复杂相互作用。这种认识可能有助于肺部疾病患者的诊断和治疗。
