TCR signaling and environment affect vasoactive intestinal peptide receptor-1 (VPAC-1) expression in primary mouse CD4 T cells

• Published in: Brain, behavior, and immunity Vol. 22; no. 7; pp. 1032 - 1040
• Main Authors: Vomhof-DeKrey, Emilie E, Hermann, Rebecca J, Palmer, Megan F, Benton, Keith D, Sandy, Ashley R, Dorsam, Sheri T, Dorsam, Glenn Paul
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.10.2008
• Subjects: Allergy and Immunology; Animals; Antibodies - pharmacology; CD4-Positive T-Lymphocytes - cytology; CD4-Positive T-Lymphocytes - drug effects; CD4-Positive T-Lymphocytes - metabolism; Cell Culture Techniques; Culture Media - pharmacology; Electrophoresis, Polyacrylamide Gel; Enzyme-Linked Immunosorbent Assay; Female; G-protein-coupled receptors; Gene Expression Regulation - drug effects; Lymphocyte Activation - drug effects; Male; Mice; Mice, Inbred C57BL; Neuropeptide; Psychiatry; Receptor-CD3 Complex, Antigen, T-Cell - immunology; Receptor-CD3 Complex, Antigen, T-Cell - physiology; Receptors, Vasoactive Intestinal Polypeptide, Type I - analysis; Receptors, Vasoactive Intestinal Polypeptide, Type I - genetics; Receptors, Vasoactive Intestinal Polypeptide, Type I - metabolism; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; RNA, Messenger - metabolism; Signal Transduction - drug effects; Signal Transduction - physiology; Src kinases; T cell signaling; Trafficking; Transcriptional regulation; Transcriptional regulation; Neuropeptide; T cell signaling; Trafficking; G-protein-coupled receptors; Src kinases
• ISSN: 0889-1591; 1090-2139
• DOI: 10.1016/j.bbi.2008.04.005

Abstract 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 24 h, 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 (24 h). 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).