IL-4 regulates VIP receptor subtype 2 mRNA (VPAC2) expression in T cells in murine schistosomiasis

Abstract

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, spleno‐cytes 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., Blum, A. M., Li, J., Elliott, D. E., and Weinstock, J. V. IL‐4 regulates VIP receptor subtype 2 mRNA (VPAC2) expression in T cells in murine schistosomiasis. FASEB J. 14, 948–954 (2000)

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