Introduction
Chronic obstructive pulmonary disease (COPD) is a chronic lung disease, characterized by persistent flow limitation and aberrant systemic inflammation ( Brightling & Greening, 2019 ; Adeloye et al., 2022 ). Smoking is one of the most well-established risk factors for COPD ( Riley & Sciurba, 2019 ; Adeloye et al., 2022 ). A growing body of evidence suggests that autoimmune response plays a fundamental role in COPD pathogenesis and has garnered significant attention ( Caramori et al., 2018 ; Hou & Sun, 2020 ). The imbalance between proinflammatory responses and immunosuppressive cells, such as MDSCs and Tregs, or cytokines to self-antigens may contribute to immune dysfunction and disease progression of COPD.

T cells are considered critical in controlling airway inflammation induced by cigarette smoke ( Caramori et al., 2018 ). Regulatory T cells (Tregs) are responsible for inhibiting T cell activation and are essential for maintaining peripheral immune homeostasis ( Sakaguchi et al., 2020 ). However, the precise role of Treg cells in the disturbed immune homeostasis of COPD has not been thoroughly investigated and the results of previous research are not entirely concordant ( Hou & Sun, 2020 ). The number of Treg cells fluctuates in both COPD patients and animal models ( Demoor et al., 2010 ; Gong et al., 2017 ; Sales et al., 2017 ). The impaired suppression of CD4 + Tcell activation and reduced IL-10 secretion may suggest the impaired function of Treg cells in COPD ( Hou & Sun, 2020 ).

PD-1 and its ligands (PD-L1/PD-L2), which play a crucial role in regulating T-cell activation and Treg cell development, have garnered considerable attention ( Gianchecchi & Fierabracci, 2018 ; Adamczyk & Krasowska, 2021 ). PD-L1 has been found to be more effective than PD-L2 in inhibiting T-cell activation and is particularly important in maintaining tissue tolerance ( Mi et al., 2021 ). PD-1/PD-L1 axis primarily maintains immunologic homeostasis under normal circumstances and mediates immune escape during the development of tumors ( Cha et al., 2019 ). PD-1-targeted antibody drugs have shown significant anti-tumor efficacy in certain solid tumors, further confirming their key role in the immune response. In contrast, studies on PD-1/PD-L1 in non-neoplastic diseases, including pulmonary inflammatory diseases, are relatively insufficient. Current research has demonstrated that PD-1/PD-L1 can be induced by inflammatory factors in chronic infectious diseases ( Chinai et al., 2015 ). Additionally, peripheral blood lymphocytes from COPD patients expressed significantly higher levels of PD-1 ( McKendry et al., 2016 ; Tan et al., 2018 ). However, the conclusions were inconsistent. Some scholars detected that the low level of PD-L1 in DCs of COPD patients might be part of the mechanisms promoting disease progression ( Stoll, Virchow & Lommatzsch, 2016 ).

The MDSCs, a type of immature myeloid cells, are known for their immunosuppressive properties ( Hegde, Leader & Merad, 2021 ). Predominantly, MDSCs are further classified into granulocyte-like MDSCs (G-MDSCs) and MNP-like MDSCs (M-MDSCs) based on their morphology and specific surface molecules ( Hegde, Leader & Merad, 2021 ). The suppressive capacity of MDSCs in inhibiting the expansion of Tregs is well-documented ( Veglia, Perego & Gabrilovich, 2018 ; Hegde, Leader & Merad, 2021 ). Numerous studies have shown that MDSCs significantly impair adaptive antitumor immunity and are closely associated with unfavorable clinical outcomes in cancer ( Veglia, Perego & Gabrilovich, 2018 ; Veglia, Sanseviero & Gabrilovich, 2021 ). However, the role of MDSCs was relatively inadequate in the case of non-neoplastic diseases, such as COPD. Additionally, the potential impact of MDSC subsets on Treg in COPD remains not yet fully understood.

Therefore, our study aimed to investigate the clinical significance of PD-1/PD-L1 axis expression, Tregs, and myeloid-derived cell subsets in the peripheral blood of COPD patients in order to explore the immuneregulatory role of MDSCs in COPD.