DataSheet_1_Extracellular ATP and Imbalance of CD4+ T Cell Compartment in Pediatric COVID-19.pdf

Severe COVID-19 in children is rare, but the reasons underlying are unclear. Profound alterations in T cell responses have been well characterized in the course of adult severe COVID-19, but little is known about the T cell function in children with COVID-19. Here, we made three major observations in a cohort of symptomatic children with acute COVID-19: 1) a reduced frequency of circulating FoxP3+ regulatory T cells, 2) the prevalence of a TH17 polarizing microenvironment characterized by high plasma levels of IL-6, IL-23, and IL17A, and an increased frequency of CD4+ T cells expressing ROR-γt, the master regulator of TH17 development, and 3) high plasma levels of ATP together with an increased expression of the P2X7 receptor. Moreover, that plasma levels of ATP displayed an inverse correlation with the frequency of regulatory T cells but a positive correlation with the frequency of CD4+ T cells positive for the expression of ROR-γt. Collectively, our data indicate an imbalance in CD4+ T cell profiles during pediatric COVID-19 that might favor the course of inflammatory processes. This finding also suggests a possible role for the extracellular ATP in the acquisition of an inflammatory signature by the T cell compartment offering a novel understanding of the involved mechanisms.

儿童重症新型冠状病毒肺炎（COVID-19）虽属罕见病症，但其潜在发病机制尚未明确。成人重症COVID-19病程中，T细胞应答的显著异常已得到充分表征，但儿童新冠患者的T细胞功能仍鲜为人知。本研究针对一组急性COVID-19有症状儿童队列开展分析，得到三项核心发现：1）循环FoxP3+调节性T细胞（regulatory T cells）的频率降低；2）存在以血浆IL-6、IL-23及IL17A水平升高为特征的TH17极化微环境，且表达ROR-γt（TH17细胞分化的核心调控因子）的CD4+ T细胞频率升高；3）血浆ATP（adenosine triphosphate，三磷酸腺苷）水平升高，同时P2X7受体（P2X7 receptor）表达上调。此外，血浆ATP水平与调节性T细胞频率呈负相关，而与表达ROR-γt的CD4+ T细胞频率呈正相关。综上，本研究数据表明，儿童新冠感染期间CD4+ T细胞亚群谱失衡，可能促进炎症进程的发展。该发现还提示，细胞外ATP可能在T细胞组分获得炎症表型的过程中发挥潜在作用，为相关发病机制提供了全新的认知视角。