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The Increased TIGIT-Expressing CD3+CD56+ Cells Are Associated with Coronary Artery Disease and Its Inflammatory Environment

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Abstract

We aimed to examine the correlation of T-cell immunoglobulin and ITIM domain (TIGIT)-expressing CD3 + CD56 + cells (TNKS) with coronary artery disease (CAD), atherosclerotic lesion progression, and inflammatory environment. A total of 199 subjects, including 98 patients with acute coronary syndrome (ACS), 52 patients with chronic coronary syndrome (CCS), and 49 control subjects, were recruited in the study. The TIGIT-expressing TNKS were quantified by flow cytometric analysis; the severity of coronary artery lesions was evaluated by the Gensini score. Whole blood cells were stimulated with interleukin-2 (IL-2), interleukin-7 (IL-7), and interleukin-15 (IL-15) in presence or absence of STAT, PI3K, and P38 MAPK inhibitors, respectively. The TIGIT-expressing TNKS was significantly increased in patients with CAD, ACS, and CCS compared to the control group (P < 0.05). The TIGIT-expressing TNKS were independent predictors of CAD, ACS and CCS (P < 0.05). The TIGIT-expressing TNKS were positively associated with Gensini score (P < 0.05). The TIGIT-expressing TNKS was positively correlated with age, and being male (P < 0.05). The inflammatory microenviroment with increased IL-2, IL-7, and IL-15 contributed to upregulation of TIGIT expression in TNKS. PI3K and P38 MAPK inhibitors could inhibit the upregulation of TIGIT expression in TNKS induced by IL-2, IL-7, and IL-15. The TIGIT-expressing TNKS may be involved in common pathogenesis of ACS and CCS, and atherosclerotic lesion progression. Meanwhile, the increased TIGIT-expressing TNKS might be associated with a proatherogenic microenvironment or inflammatory microenvironment. PI3K and P38 MAPK signaling pathways were involved in the regulation of TIGIT expression.

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Data Availability

The data presented in this study are available on reasonable request from the corresponding author.

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Funding

This work was supported in part by grants from the National Natural Science Foundation of China (Nos. 82160086 and 81960047), China Postdoctoral Science Foundation(2022MD723769), the Science and Technology Fund of Guizhou Province (No. qiankehepingtairencai-GCC[2022]040-1, qiankehezhicheng[2019]2800, qiankehejichu-ZK[2022]zhongdian043, qiankehechengguo-LC[2022]013), the Health and Family Planning Commission of Guizhou Province (qianweijianhan[2021]160), Provincial Key Medical Subject Construction Project of Health Commission of Guizhou Province and the National Key Medical Subject Construction Project of National Health Commission of China, Health Commission of Guizhou Province (gzwkj2021-357).

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Conceptualization, X.L.X., Z.H.L, W.L.; methodology, X.L.X., H.Y.Z; software, X.L.X.; validation, X.L.X., H.Y.Z., Z.G.D., G.W.H.; formal analysis, X.L.X., Y.Z.J.,L,N.; investigation, X.L.X., Z.H.L., L.N., Z.G.D.; resources, W.L.; data curation, Y.Z.J., X.L.X.,Z.G.D., G.W.H.; writing—original draft preparation, X.L.X.; writing—review and editing, X.L.X., Z.H.L., W.L.; supervision, H.Y.Z.; project administration, W.L.; funding acquisition, W.L., Z.H.L. All authors reviewed the manuscript.

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Correspondence to Zhenhua Luo or Wei Li.

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Xiong, X., Duan, Z., Zhou, H. et al. The Increased TIGIT-Expressing CD3+CD56+ Cells Are Associated with Coronary Artery Disease and Its Inflammatory Environment. Inflammation 46, 2024–2036 (2023). https://doi.org/10.1007/s10753-023-01859-6

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