Immunoeffector and immunoregulatory activities of vasoactive intestinal peptide.
Vasoactive intestinal peptide (VIP) and its two G protein-coupled receptors, VPAC1R and VPAC2R, are prominent in the immune system and potently affect T cells and macrophages. VPAC1Rs are expressed constitutively by blood and tissue T cells, with an order of prevalence of Th2>Th1>>Ts, and transmit signals suppressive for migration, proliferation and cytokine production. Immune activation of T cells downregulates VPAC1Rs and upregulates VPAC2Rs. VPAC2Rs mediate T cell chemotaxis, stimulation of some Th2-type cytokines, and inhibition of some Th1-type cytokines. A tentative hypothesis that the VIP-VPAC2R axis is the major neuroregulator of Th2/Th1 balance has been confirmed by finding an increased ratio in CD4 T cells of transgenic (TG) mice, expressing high levels of VPAC2Rs, and a decreased ratio in CD4 T cells of VPAC2R-null (K/O) mice. VPAC2R TG mice exhibit an allergic phenotype, whereas the K/O mice are hypoallergic and have heightened delayed-type hypersensitivity. The mechanisms of VIP-VPAC2R effects include decreased Th2 apoptosis, increased Th2-type cytokine production, and greater generation of Th2 memory cells. VPAC2R antagonists are being developed to alleviate allergic diseases and strengthen effector Th1 cell-mediated immunoprotection.
Voice
Julia K
JK
Department of Medicine, University of California, San Francisco, CA 94143, USA.
Dorsam
Glenn
G
Chan
Robert C
RC
Grinninger
Carola
C
Kong
Yvonne
Y
Goetzl
Edward J
EJ
D000818:Animals; D002454:Cell Differentiation; D006801:Humans; D018005:Receptors, Vasoactive Intestinal Peptide / Q000235:genetics / Q000378:metabolism; D051239:Receptors, Vasoactive Intestinal Peptide, Type II; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology; D014660:Vasoactive Intestinal Peptide / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology
D018005:Receptors, Vasoactive Intestinal Peptide; D051239:Receptors, Vasoactive Intestinal Peptide, Type II; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I; D014660:Vasoactive Intestinal Peptide