Voice J K, Dorsam G, Lee H, Kong Y, Goetzl E J
Departments of Medicine and Microbiology-Immunology, University of California Medical Center, San Francisco, California 94143-0711, USA.
FASEB J. 2001 Nov;15(13):2489-96. doi: 10.1096/fj.01-0671com.
Vasoactive intestinal peptide (VIP) and its G-protein-coupled receptors (VPAC1 and VPAC2 Rs) are prominent in the immune system. In T cells, VPAC1 R is expressed constitutively whereas VPAC2 R is induced only after stimulation of the T cell receptor (TCR) or exposure to some cytokines. VPAC1 R and VPAC2 R also transduce different effects of VIP on T cells. Constitutive expression of VPAC2 R selectively in CD4+ T cells (helper-inducer Th cells) of transgenic (TG) C57BL/6 mice directed by the lck tyrosine kinase promoter is now shown to evoke production of more Th2-type interleukins 4 and 5, and less Th1-type interferon gamma after TCR activation. VPAC2 R TG mice consequently have significant elevations of blood IgE, IgG1, and eosinophils. VPAC2 R TG mice also show increased IgE antibody responses, which mediate heightened cutaneous allergic reactions, and have depressed delayed-type hypersensitivity. VIP enhancement of the ratio of Th2 cell to Th1 cell cytokines thus evokes an allergic state in normally nonallergic mice, which suggests the possibility of neuropeptide contributions to immune phenotypic alterations in human hypersensitivity diseases.
血管活性肠肽（VIP）及其G蛋白偶联受体（VPAC1和VPAC2受体）在免疫系统中很突出。在T细胞中，VPAC1受体组成性表达，而VPAC2受体仅在T细胞受体（TCR）受到刺激或暴露于某些细胞因子后才被诱导表达。VPAC1受体和VPAC2受体也介导VIP对T细胞的不同作用。现在发现，由lck酪氨酸激酶启动子指导，在转基因（TG）C57BL/6小鼠的CD4+T细胞（辅助诱导性Th细胞）中选择性组成性表达VPAC2受体，会在TCR激活后引发更多的Th2型白细胞介素4和5的产生，以及更少的Th1型干扰素γ的产生。因此，VPAC2受体转基因小鼠的血液中IgE、IgG1和嗜酸性粒细胞显著升高。VPAC2受体转基因小鼠还表现出IgE抗体反应增加，这介导了皮肤过敏反应的增强，并且迟发型超敏反应受到抑制。因此，VIP增加Th2细胞与Th1细胞细胞因子的比例在正常无过敏反应的小鼠中引发了过敏状态，这表明神经肽可能在人类超敏反应疾病的免疫表型改变中发挥作用。
