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Updated: Jul 4, 2026

Phenotypic and Functional Analysis of Activated Regulatory T Cells Isolated from Chronic Lymphocytic Choriomeningitis Virus-infected Mice
Published on: June 22, 2016
Stimulatory and suppressive signal transduction regulates vasoactive intestinal peptide receptor-1 (VPAC-1) in
Emilie E Vomhof-DeKrey1, Glenn Paul Dorsam1
1Department 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.
Abstract:
Vasoactive intestinal peptide receptor-1 (VPAC-1) is an anti-proliferative, G-protein coupled receptor that is highly expressed on naïve T cells, and has been reported to be downregulated upon T cell activation. The T cell signaling molecules involved in mediating low VPAC-1 levels have not been identified. Therefore, to gain a greater understanding into this regulation, this study investigated the signaling pathways that regulate (VPAC-1) in murine, primary CD4 T cells. To this end, murine, splenic CD4 T cells were pretreated separately with 10 different pharmacological inhibitors and incubated +/- anti-CD3 for 24h. Total RNA was isolated, and VPAC-1 mRNA levels were measured by qPCR. Our results support that JNK kinases, downstream from the protein kinase, Zap70, are involved in suppressive regulation of VPAC-1 steady-state mRNA levels after anti-CD3 treatment. In contrast, inhibitors against PKC, ERK, p38, Zap70 and Rac1 supported a stimulatory influence in VPAC-1 regulation in the absence of T cell signaling. By studying the signaling pathways that regulate VPAC-1 in T cells, we can gain greater insight into the role of this anti-inflammatory receptor in autoimmunity and infectious diseases.
Insights
This study reveals that JNK kinases suppress Vasoactive intestinal peptide receptor-1 (VPAC-1) mRNA levels in T cells upon activation. Other signaling pathways, like PKC and ERK, stimulate VPAC-1 in the absence of T cell signaling.
Area of Science:
- Immunology
- Cell Signaling
Background:
- Vasoactive intestinal peptide receptor-1 (VPAC-1) is a G-protein coupled receptor expressed on T cells.
- VPAC-1 is downregulated upon T cell activation, but the underlying signaling pathways remain unclear.
Purpose of the Study:
- To investigate the signaling pathways regulating VPAC-1 expression in murine CD4 T cells.
- To identify molecules involved in the downregulation of VPAC-1 during T cell activation.
Main Methods:
- Murine splenic CD4 T cells were treated with pharmacological inhibitors.
- Cells were stimulated with anti-CD3 antibody for 24 hours.
- VPAC-1 mRNA levels were quantified using qPCR.
Main Results:
- JNK kinases, downstream of Zap70, suppress VPAC-1 mRNA levels following anti-CD3 stimulation.
- Inhibitors of PKC, ERK, p38, Zap70, and Rac1 indicated a stimulatory role in VPAC-1 regulation without T cell signaling.
Conclusions:
- JNK signaling pathway plays a suppressive role in VPAC-1 regulation post-T cell activation.
- Understanding VPAC-1 regulation offers insights into its role in inflammatory and autoimmune diseases.
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