The correlation of tolerangenic TIGIT+NK cells with the severity of COPD

<bold>Background:</bold> Our study has shown reduced tolerangenic PD-L1⁺ cDC1 is associated with lung function decline through enhancing Th17 immunity. Other inhibitoy immune checkpoints contribute to the feature of autoimmunity in COPD remains unclear <bold>Objective:</bold> To explore tolerangenic role of immune cells regulated by inhibitory immune checkposints other than PD-1/PD-L1 axis in COPD <bold>Methods:</bold> We performed multicolar flow cytometry analysis on PBMCs from 3 healthy subjects and COPD patients. These analyzes include immune cells (monoctye, NK, NKT, T and B cell) and inhibitory immune checkpoints (PD-1, CTLA-4, LAG-3, TIM-3, TIGIT). We then used t-SNE method to serch for different clusters of tolerangeic immune cells between normal and COPD participants. Finally, we increased N number to validate the different expression of newly discovered tolerangenic immune cell between normal and CODP subjects and its clinical relevance in COPD <bold>Results:</bold> TIGIT⁺NK cells were shown significant differently expressed on PBMCs from normal and COPD participants by analyzed results of t-SNE (Fig. 1A-B). A total of 36 participants (health, n=14; COPD, n=22) were then enrolled to validate. A trend of reduced TIGIT⁺NK in PBMC, particular in TIGIT⁺NK^dim (statistically significant) were found in COPD (Fig. 2A).. To further investigate the clinical impact of reduced TIGIT⁺NK cells on COPD, our data demonstrated the TIGIT⁺NK cells were positive corelation to post-BD FEV1 (%) (Fig. 2B). This suggest loss of tolerangenic NK cells regulated by TIGIT may be related to the severity of COPD. <bold>Conclusions:</bold> Our study showed reduced circulating TIGIT⁺NK cells and its subtypes in COPD patients and the decreased TIGIT⁺NK may be related to the severity of COPD.