Reduced Tolerogenic Program Death-Ligand 1 (PD-L1)-expressed Conventional Type 1 Dendritic cells (cDC1) Is Associated with A Rapid Decliner Phenotype of Chronic Obstructive Pulmonary Disease (COPD)

Background Chronic obstructive pulmonary disease (COPD) is characterized, at least in part, by autoimmunity through amplified T helper 1 and 17 (Th1 and Th17) immune response. Loss of immune tolerance controlled by programed death ligand 1 (PD-L1) may contribute to it Objectives We studied the tolerogenic role of PD-L1+dendritic cells (DCs) and its subtypes in relation to specific T cell immunity and clinical phenotypes of COPD. Methods We used flow cytometry to analyzed PD-L1 expression on DC and its subtypes in peripheral blood mononuclear cells (PBMCs) from normal and COPD participants. T cells proliferation and signature cytokines of T cell subtypes stimulated with elastin as autoantigens were measured by flow cytometry and enzyme-linked immunosorbent assays (ELISA), respectively Measurement and main results A total of 83 participants were enrolled (normal, n = 29; COPD, n = 54). Reduced PD-L1 ⁺ conventional dendritic cell 1 (cDC1) in PBMCs of COPD patients was shown (13.7± 13.7%, P = 0.03). The decrease in PD-L1 ⁺ cDC1 was associated with a rapid decliner phenotype of COPD ( P = 0.02) and correlated with CD4 ⁺ T cells ( r =-0.33, P =0.02). Functionally, PD-L1 blockade enhanced CD4 ⁺ T cells proliferation stimulated with CD3/elastin (31.2±22.3%, P =0.04) and interleukin (IL)-17A production with both CD3 (156.3±54.7, P =0.03) and CD3/elastin (148±64.9, P =0.03) from normal PBMCs. PD-L1 blockade failed to increase IL-17A production in cDC1-depleted PBMCs. By contrast, there was no significant change in interferon (IFN)-γ, IL-4, and IL-10 after PD-L1 blockade. Conclusion Circulating PD-L1 ⁺ cDC1 was reduced in COPD, which the tolerogenic role was suppressed with susceptibility to self-antigens and linked to a rapid decliner phenotype through Th17-skewed chronic inflammation.