Specific induction of the unique GPR15 expression in heterogeneous blood lymphocytes by tobacco smoking

Purpose: In the peripheral blood, it has been shown that smoking is, to date, the only specific condition leading to an increase in GPR15+ T cells. We, therefore, aimed to characterize GPR15-expressing blood T cells in more detail. Materials and Methods: The whole transcriptome by RNAseq as a proxy for protein expression was analyzed in GPR15+ and GPR15- T cells. A deep immuno-phenotyping was conducted for the identification of T cell subtypes. Results: The expression of GPR15 seemed to be unique, not concomitantly accompanied with the expression of another protein. According to different T cell subtypes, there is no single cell type prominently represented in GPR15+ T cells. The individually different proportions of GPR15+ cells among each GPR15-expressing T cell subtypes in blood were strongly associated with chronic smoking. Indeed, the frequency of GPR15+ T cell subtypes can be effectively used as a highly convincing biomarker for tobacco smoking. Conclusions: While the chronic smoking-induced enrichment of GPR15+ T cells in blood might indicate a systemic inflammation, by the widespread presence in different T cell subtypes, GPR15 could feature a general impact on maintaining the systemic homeostasis to putatively prevent harm from smoking.

研究目的：目前已有研究证实，在外周血中，吸烟是迄今为止唯一可特异性导致GPR15阳性T细胞比例升高的因素。本研究旨在更深入地表征表达GPR15的外周血T细胞。
材料与方法：通过RNA测序（RNAseq）获取全转录组数据，以其作为蛋白质表达的替代指标，对GPR15阳性与GPR15阴性T细胞进行分析；同时开展深度免疫表型分型，以鉴定T细胞亚群。
结果：GPR15的表达具有独特性，未伴随其他蛋白的共表达。在不同T细胞亚群中，并无某一单一群落在GPR15阳性T细胞中占绝对优势。血液中各GPR15阳性T细胞亚群内GPR15+细胞的个体间比例差异，与慢性吸烟行为存在显著关联。事实上，GPR15阳性T细胞亚群的频率可作为烟草暴露的高可信度生物标志物。
结论：尽管慢性吸烟诱导外周血中GPR15阳性T细胞富集这一现象可能提示全身性炎症反应，但鉴于GPR15广泛存在于多种T细胞亚群中，其或可通过维持系统稳态，潜在地抵御吸烟带来的机体损伤。