Abstract：
Members of the vanin gene family include VNN1, VNN2 and VNN3 in humans. Although the functions of vanins have been widely examined in myeloid cells, their expression and functions have not been clarified in T lymphocytes. This study aimed to elucidate the significance of Vanin-2 (VNN2) on human peripheral blood T lymphocytes and study its expression in systemic lupus erythematosus (SLE). The differential expression of Vanins was analysed by bioinformatics. VNN2 expressions in peripheral blood T cell subsets were analysed by single-cell RNA sequencing data and flow cytometry. Changes of VNN2 expression before and after T cell activation were further clarified by western blot. The function of VNN2+ cells was studied by granzyme B and perforin detection. Changes in VNN2+ proportions in T cell subsets of SLE patients were further analysed. In the present study, only VNN2 among vanins showed distinguishable expression in T cells. VNN2+ percentages were higher in CD8+ T cells than in CD4+ T cells. VNN2+ T cells were with a higher memory T cell composition. VNN2 expression was significantly increased after T cell stimulation. VNN2+ T cells had higher levels of granzyme B and perforin secretion than VNN2- T cells. Clinically, VNN2+ percentages in T cells of SLE patients were upregulated. Together, these data suggested that VNN2 is expressed in peripheral blood T cells characterized more granzyme B and perforin secretion, and increased VNN2+ T cells in SLE patients could reflect altered T cell functions in vivo.
摘要：
vanin基因家族的成员包括人类中的VNN1、VNN2和VNN3。尽管vanins的功能已在骨髓细胞中得到广泛研究，其在T淋巴细胞中的表达和功能尚未明确。本研究旨在阐明Vanin-2（VNN2）在人外周血T淋巴细胞上的意义，并研究其在系统性红斑狼疮（SLE）中的表达。通过生物信息学分析了Vanins的差异表达。通过单细胞RNA测序数据和流式细胞术分析外周血T细胞亚群中的VNN2表达。通过蛋白质印迹进一步阐明了T细胞活化前后VNN2表达的变化。通过颗粒酶B和穿孔素检测研究了VNN2细胞的功能。进一步分析SLE患者T细胞亚群中VNN2+比例的变化。在本研究中,vanins中只有VNN2在T细胞中显示出可区分的表达。CD8+T细胞中的VNN2+百分比高于CD4+T细胞。VNN2+T细胞具有较高的记忆T细胞组成。T细胞刺激后VNN2表达显著增加。VNN2+T细胞的颗粒酶B和穿孔素分泌水平高于VNN2-T细胞。临床上,SLE患者T细胞中的VNN2+百分比上调。一起,这些数据表明，VNN2在外周血T细胞中表达，其特征是更多的颗粒酶B和穿孔素分泌，SLE患者中VNN2T细胞的增加可以反映体内T细胞功能的改变。
