■IL-2Rα敲除(KO)小鼠已有助于发现IL-2Rα的免疫调节特性。虽然最初只认为是一种刺激性细胞因子,IL-2和IL-2RαKO小鼠表明,这种细胞因子受体系统通过再刺激诱导的细胞死亡和促进T调节性细胞的存活来控制免疫反应。虽然主要在淋巴细胞的背景下描述,我们实验室最近的研究表明,IL-2R在平滑肌细胞中表达。鉴于这一发现,我们试图使用IL-2RαKO来确定该受体在血管平滑肌细胞中的功能。令人惊讶的是,我们发现IL-2RαKO血管平滑肌细胞具有可检测的IL-2Rα。
■我们使用基于多种基因和蛋白质的方法来确定为什么IL-2RαKO血管平滑肌细胞表现出IL-2Rα蛋白。这些方法包括:基因组测序,评估细胞和组织的母体微嵌合体的证据,并测定IL-2Rα蛋白的半衰期。
■我们的研究证明了以下几点:(1)除了细胞表面,IL-2Rα定位于细胞核;(2)IL-2RαKO小鼠中IL-2Rα基因缺失完整;(3)IL-2RαKO和WT组织均显示母体微嵌合的证据,IL-2Rα的可能来源(4)IL-2Rα在细胞之间传递;(5)IL-2Rα具有长的半衰期;和(6)核IL-2Rα有助于调节细胞增殖和大小。
■我们的发现表明,完全IL-2Rα丢失的表型比IL-2RαKO小鼠所证明的更严重,IL-2Rα在调节非淋巴样细胞中的细胞增殖中起着迄今未被认识的作用。
UNASSIGNED: IL-2Rα knock out (KO) mice have been instrumental to discovering the immunoregulatory properties of IL-2Rα. While initially thought of only as a stimulatory cytokine, IL-2 and IL-2Rα KO mice revealed that this cytokine-receptor system controls immune responses through restimulation-induced cell death and by promoting the survival of T regulatory cells. Although described mostly in the context of lymphocytes, recent studies by our laboratory showed that IL-2R is expressed in smooth muscle cells. Given this finding, we sought to use IL-2Rα KO to determine the function of this receptor in vascular smooth muscle cells. Surprisingly, we found that IL-2Rα KO vascular smooth muscle cells had detectable IL-2Rα.
UNASSIGNED: We used multiple gene and protein-based methods to determine why IL-2Rα KO vascular smooth muscle cells exhibited IL-2Rα protein. These methods included: genomic sequencing, assessing cells and tissues for evidence of maternal microchimerism, and determining the half-life of IL-2Rα protein.
UNASSIGNED: Our studies demonstrated the following: (1) in addition to the cell surface, IL-2Rα is localized to the
nucleus; (2) the genetic deletion of IL-2Rα is intact in IL-2Rα KO mice; (3) both IL-2Rα KO and WT tissues show evidence of maternal microchimerism, the likely source of IL-2Rα (4) IL-2Rα is transmitted between cells; (5) IL-2Rα has a long half-life; and (6) nuclear IL-2Rα contributes to the regulation of cell proliferation and size.
UNASSIGNED: Our findings suggest that the phenotype of complete IL-2Rα loss is more severe than demonstrated by IL-2Rα KO mice, and that IL-2Rα plays a here-to-fore unrecognized role in regulating cell proliferation in non-lymphoid cells.