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Cytokine storm promoting T cell exhaustion in severe COVID-19 revealed by single cell sequencing data analysis

Precision Clinical Medicine 2022年第2期5卷 87-99页

作者： Minglei Yang Chenghao Lin Yanni Wang Kang Chen Yutong Han Haiyue Zhang Weizhong Li Zhongshan School of Medicine Sun Yat-sen UniversityGuangzhou 510080China Center for Precision Medicine Sun Yat-sen UniversityGuangzhou 510080China Key Laboratory of Tropical Disease Control of Ministry of Education Sun Yat-Sen UniversityGuangzhou 510080China

Background:Evidence has suggested that cytokine storms may be associated with T cell exhaustion(TEX)in ***,the interaction mechanism between cytokine storms and TEX remains ***:With the aim of dissecting the molecular relationship of cytokine storms and TEX through single-cell RNA sequencing data analysis,we identified 14 cell types from bronchoalveolar lavage fluid of COVID-19 patients and healthy *** observed a novel subset of severely exhausted CD8 T cells(Exh T_CD8)that co-expressed multiple inhibitory receptors,and two macrophage subclasses that were the main source of cytokine storms in ***:Correlation analysis between cytokine storm level and TEX level suggested that cytokine storms likely promoted TEX in severe ***–cell communication analysis indicated that cytokines(***10,CXCL11,CXCL2,CCL2,and CCL3)released by macrophages acted as ligands and significantly interacted with inhibitory receptors(***3,DPP4,CCR1,CCR2,and CCR5)expressed by Exh T_*** interactions formed the cytokine–receptor axes,which were also verified to be significantly correlated with cytokine storms and TEX in lung squamous cell ***:Cytokine storms may promote TEX through cytokine-receptor axes and be associated with poor prognosis in *** cytokine-receptor axes may reverse *** finding provides novel insights into TEX in COVID-19 and new clues for cytokine-targeted immunotherapy development.

关键词： COVID-19 immune exhaustion cytokine storm single-cell sequencing data analysis T cell immune checkpoint

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