Vomhof-DeKrey Emilie E, Hermann Rebecca J, Palmer Megan F, Benton Keith D, Sandy Ashley R, Dorsam Sheri T, Dorsam Glenn Paul
Department of Chemistry and Molecular Biology, The Center for Protease Research, North Dakota State University, Room 320, IACC Building, 1320 Albrecht Boulevard, Fargo, ND 58105, USA.
Department of Chemistry and Molecular Biology, The Center for Protease Research, North Dakota State University, Room 320, IACC Building, 1320 Albrecht Boulevard, Fargo, ND 58105, USA.
Brain Behav Immun. 2008 Oct;22(7):1032-1040. doi: 10.1016/j.bbi.2008.04.005. Epub 2008 Jun 4.
Strict regulation of T cell function is imperative to control adaptive immunity, and dysregulation of T cell activation can contribute to infectious and autoimmune diseases. Vasoactive intestinal peptide receptor-1 (VPAC-1), an anti-inflammatory G-protein coupled receptor, has been reported to be downregulated during T cell activation. However, the regulatory mechanisms controlling the expression of VPAC-1 in T cells are not well understood. Therefore, mouse splenic CD4 T cells were treated in complete media+/-anti-CD3 for 24h, total RNA isolated and VPAC-1 levels measured by qPCR. Surprisingly, we discovered that T cells incubated in complete media steadily upregulated VPAC-1 mRNA levels over time (24h). Importantly, CD4 T cells isolated from blood also showed elevated VPAC-1 expression compared to splenic T cells. Collectively, these data support that the vascular environment positively influences VPAC-1 mRNA expression that is negatively regulated by TCR signaling. This research was supported by a national service award (1KO1 DK064828) to G.D., the Center for Protease Research (2P20RR015566), and INBRE (P20 RR016741).
严格调控T细胞功能对于控制适应性免疫至关重要，而T细胞活化失调会导致感染性疾病和自身免疫性疾病。血管活性肠肽受体-1（VPAC-1）是一种抗炎性G蛋白偶联受体，据报道在T细胞活化过程中表达下调。然而，控制T细胞中VPAC-1表达的调控机制尚不清楚。因此，将小鼠脾脏CD4 T细胞在完全培养基中用抗CD3处理或不处理24小时，分离总RNA并通过qPCR测量VPAC-1水平。令人惊讶的是，我们发现，在完全培养基中孵育的T细胞随着时间推移（24小时）VPAC-1 mRNA水平稳步上调。重要的是，与脾脏T细胞相比，从血液中分离的CD4 T细胞也显示出VPAC-1表达升高。总体而言，这些数据支持血管环境对VPAC-1 mRNA表达产生正向影响，而VPAC-1 mRNA表达受到TCR信号的负调控。本研究得到了授予G.D.的一项国家服务奖（1KO1 DK064828）、蛋白酶研究中心（2P20RR015566）和印第安纳临床与转化科学研究所网络（P20 RR016741）的支持。
