IL-4 regulates VIP receptor subtype 2 mRNA (VPAC2) expression in T cells in murine schistosomiasis.
In murine schistosomiasis, granuloma T cells express VPAC2 mRNA, whereas there is none in splenocytes. This suggests that T cell VPAC2 mRNA is inducible. To address this issue, splenocytes from schistosome-infected mice were incubated with anti-CD3 to induce VPAC2 mRNA, which only appeared when cell cultures also contained anti-IL-4 mAb. Granuloma cells expressed VPAC2 mRNA. This natural expression decreased substantially when cells were cultured 3 days in vitro. However, granuloma cells cultured with anti-IL-4 mAb strongly expressed VPAC2 mRNA. IL-4 KO mice were examined to further address the importance of IL-4 in VPAC2 regulation. Splenocytes and dispersed granuloma cells from IL-4 KO animals had substantially more VPAC2 mRNA than those in wild-type controls. VPAC2 mRNA content decreased when cells were cultured with rIL-4. VPAC2 mRNA localized to CD4+ T cells. Th1 cell lines expressed VPAC2 mRNA much stronger than Th2 cells. Anti-IL-4 mAb increased VPAC2 mRNA expression in Th2 cells cultured in vitro. However, rIL-4 could not suppress VPAC2 mRNA expression in Th1 cells. Thus, VPAC2 is an inducible CD4+ T cell receptor, and IL-4 down-modulates VPAC2 mRNA expression in Th2 cells.
Metwali
A
A
Division of Gastroenterology-Hepatology, Department of Internal Medicine, University of Iowa, Iowa City, Iowa 52242, USA.
Blum
A M
AM
Li
J
J
Elliott
D E
DE
Weinstock
J V
JV
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D002460:Cell Line; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology / Q000502:physiology*; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics*; D018005:Receptors, Vasoactive Intestinal Peptide / Q000235:genetics* / Q000378:metabolism; D051239:Receptors, Vasoactive Intestinal Peptide, Type II; D012552:Schistosomiasis / Q000235:genetics*; D013601:T-Lymphocytes / Q000378:metabolism*; D018417:Th1 Cells / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism
D000911:Antibodies, Monoclonal; D012333:RNA, Messenger; D018005:Receptors, Vasoactive Intestinal Peptide; D051239:Receptors, Vasoactive Intestinal Peptide, Type II; D015847:Interleukin-4