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).

Vasoactive intestinal peptide (VIP) is a pleiotropic secretagogue involved in crucial biological processes necessary for life. Its biological effects are mediated by two structurally similar integral membrane receptors called vasoactive intestinal peptide receptor‐1 and 2 (VPACR‐1/2). VPACR‐1 is a member of the group IIA G protein coupled receptors (GPCR) which are characterized by 7 transmembrane domains (7TM). VIP binding to VPACR‐1 elicits adenylate cyclase/cAMP/PKA and phospholipase C/D signaling cascades. VPACR‐1 has a wide expression profile in the mouse, including the nervous and immune systems. Recently, a novel VPACR‐1 isoform was identified that lacks exons 10 and 11 to form a 5 transmembrane receptor (5TM), and in contrast, elicits significant tyrosine phosphorylation through a G protein independent mechanism. The biological effects mediated by this recently discovered non‐GPCR linked isoform, 5TM, are not known. To determine the expression profile of this isoform, mRNA will be collected from various mouse tissues, cDNA generated with anchored primers and the expression profile of the 7TM and 5TM quantitated using qPCR. Identifying which mouse tissues express the 5 TM VPACR‐1 isoform is a major first step in understanding its contribution to cellular function and physiology. Supported by NIH‐KO1 1K01DK064828 and COBRE 2P20RR05566.