A causal relationship between circulating immune cells, plasma metabolites, and pulmonary diseases: a mediated Mendelian randomization study.

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.