Immunosuppression by Inflammation-Stimulated Amplification of Myeloid-Derived Suppressor Cells and Changes in Expression of Immune Checkpoint HHLA2 in Chronic Obstructive Pulmonary Disease

Abstract

Background

The interaction between immune checkpoint and myeloid-derived suppressor cells (MDSCs) play a significant role in inflammatory diseases. But their correlation with chronic obstructive pulmonary disease (COPD) remains unclear.

Methods

The differentially expressed immune checkpoints and immunocytes in the airway tissues of COPD patients were identified by bioinformatics analysis, followed by correlation analysis and identification of immune-related differential genes for Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analysis. The results of bioinformatics analysis were verified by ELISA and Real-Time PCR and transcriptome sequencing of the peripheral blood of both COPD patients and healthy subjects.

Results

The results of the bioinformatics analysis showed that the level of MDSCs in airway tissue and peripheral blood of COPD patients was higher than that of healthy controls. The expression of CSF1 in airway tissue and peripheral blood of COPD patients increased, and CYBB was increased in airway tissue and decreased in peripheral blood of COPD patients. The expression of HHLA2 in the airway tissue decreased in COPD patients, and showed a negative correlation with MDSCs, with a correlation coefficient of −0.37. The peripheral blood flow cytometry results indicated that MDSCs and Treg cells of COPD patients were higher than those in the healthy control group. The results of peripheral blood ELISA and RT-PCR showed that the HHLA2 and CSF1 levels in COPD patients were higher than those in the healthy control group.

Conclusion

In COPD, the bone marrow is stimulated to produce MDSCs, and a large number of MDSCs migrate to airway tissue through peripheral blood and cooperate with HHLA2 to exert an immunosuppressive effect. Whether MDSCs play an immunosuppressive effect during migration needs to be further confirmed.

Keywords:

• chronic obstructive pulmonary disease
• COPD
• myeloid-derived suppressor cell
• MDSC
• immunosuppression
• human endogenous retrovirus-H long terminal repeat-associating protein 2
• HHLA2
• bioinformatics analysis

Acknowledgments

This work was supported by the Natural Science Foundation of Xinjiang Uygur Autonomous Region [project numbers:2022D01E28]; the Natural Science Foundation of Xinjiang Uygur Autonomous Region [project numbers: 2022D01C179]; Xinjiang Key Laboratory of Pulmonary Disease Research Fund [project numbers: ZYYHX202103]; the National Natural Science Foundation of China [project numbers: 82160844].

Disclosure

The authors report no conflicts of interest in this work.