Primary role for Gi protein signaling in the regulation of interleukin 12 production and the induction of T helper cell type 1 responses.
Primary role for Gi protein signaling in the regulation of interleukin 12 production and the induction of T helper cell type 1 responses.
复制标题
GI蛋白信号传导的主要作用在白介素12产生和T辅助细胞1型反应的诱导中的主要作用。
DOI：
10.1084/jem.191.9.1605
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发表时间：
2000-05-01
影响因子：
15.3
通讯作者：
Kelsall, B L
中科院分区：
文献类型：
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作者：
He, J;Gurunathan, S;Iwasaki, A;Ash-Shaheed, B;Kelsall, B L
我们探讨了GI蛋白信号在调节白细胞介素12(IL-12)产生和辅助性T细胞1型(Th1)T细胞分化中的作用。在最初的研究中，我们表明，用百日咳毒素(PT)处理正常小鼠，可以增强脾细胞对微生物和非微生物刺激产生IL-12的能力。此外，PT还可增加刺激细胞产生肿瘤坏死因子-α和IL-10。未经治疗的α2/−小鼠表现出脾细胞产生IL-12和肿瘤坏死因子-α，以及纯化的脾α+树突状细胞产生IL-12p40。最后，我们发现，虽然感染大利什曼原虫的正常BALB/c小鼠表现出不愈合的表型，但在感染开始时接受PT治疗的小鼠表现出愈合的表型，同时引流淋巴结中利什曼原虫特异性Th1反应增强。此外，联合应用抗IL-12和PT可阻止愈合。这些数据表明，内源性GI蛋白信号在体内调节IL-12的产生和诱导Th1反应中起主要作用。
We explored the role of Gi protein signaling in the regulation of interleukin (IL)-12 production and T helper cell type 1 (Th1) T cell differentiation. In initial studies, we showed that treatment of normal mice with pertussis toxin (PT), which inhibits Gi protein signaling, enhanced the capacity of splenocytes to produce IL-12 in response to both microbial and nonmicrobial stimuli. In addition, PT treatment increased the production of tumor necrosis factor (TNF)-α and IL-10 by stimulated cells. These findings were corroborated by the fact that untreated Gi2α2/− mice exhibited enhanced production of IL-12 and TNF-α by splenocytes, and of IL-12 p40 by purified spleen CD8α+ lymphoid dendritic cells. Finally, we showed that while normal BALB/c mice infected with Leishmania major exhibited a nonhealing phenotype, those treated with PT when infection was initiated exhibited a healing phenotype along with an enhancement of leishmania-specific Th1 responses in draining lymph nodes. Further, healing was prevented by coadministration of anti–IL-12 and PT. These data demonstrate that endogenous Gi protein signaling has a primary role in the regulation of IL-12 production and the induction of Th1 responses in vivo.