HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Huang, M.-C. Articles by Goetzl, E. J. Search for Related Content PubMed PubMed Citation Articles by Huang, M.-C. Articles by Goetzl, E. J.

Differential Signaling of T Cell Generation of IL-4 by Wild-Type and Short-Deletion Variant of Type 2 G Protein-Coupled Receptor for Vasoactive Intestinal Peptide (VPAC₂)¹

Mei-Chuan Huang^*, Allison L. Miller^*, Wengang Wang^*, Yvonne Kong^*, Sudhir Paul and Edward J. Goetzl^2,*

^* Departments of Medicine and Microbiology-Immunology, University of California, San Francisco, CA 94143; and Departments of Pathology and Laboratory Medicine, University of Texas Health Science Center, Houston, TX 77030

Vasoactive intestinal peptide (VIP) released from some neurons and T cells affects T cell migration, cytokine generation, and other functions by binding to constitutively expressed type 1 G protein-coupled receptor (VPAC₁) or activation-induced type 2 G protein-coupled receptor (VPAC₂). Recently, a short-deletion (SD) splice variant of mouse VPAC₂ that lacks 14 amino acids at the end of the last transmembrane domain has been identified in T cells and shown to resemble wild-type (WT) VPAC₂ in affinity of VIP binding but to differ by lack of signaling of T cell adenylyl cyclase, migration, and IL-2 secretion. As Th2 cells are the principal source of immune VIP and have the greatest functional responses to VIP, the differences in signals transduced by WT and SD VPAC₂ were studied in VPAC₂–low D10G4.1 model Th2 cell transfectants individually expressing the respective types of VPAC₂ equally. WT and SD VPAC₂ Th2 cell transfectants secreted equal amounts of VIP. WT VPAC₂ transfectants generated more IL-4 than did SD VPAC₂ transfectants, and this increment was dependent on endogenous VIP. Exogenous VIP further increased IL-4 production by WT VPAC₂ transfectants but decreased IL-4 production by SD VPAC₂ transfectants. Cotransfection of the two constructs diminished VIP enhancement of IL-4 production seen with WT VPAC₂ alone by preventing increases in nuclear levels of the requisite transcription factors c-Maf and Jun B. Thus the ratio of two forms of T cell VPAC₂ determines the net effect of VIP on IL-4 generation by activated Th2 cells.