A novel VIP signaling pathway in T cells: cAMP → protein tyrosine phosphatase (SHP-2?) → JAK2/STAT4 → Th1 differentiation
- 作者：Li Liu ; Jui-Hung Yen ; Doina Ganea
- 关键词：Vasoactive intestinal peptide ; Th1 differentiation ; Jak2/STAT4 signaling pathway ; Protein tyrosine phosphatases (PTP) ; SHP-2 protein tyrosine phosphatase
- 刊名：Peptides
- 出版年：2007
- 期刊代码：59_01969781
- 类别：neu
- 出版时间：September 2007
- 卷：28
- 期：9
- 页码：1814-1824
- 文件大小：1343 K
摘要
Vasoactive intestinal peptide (VIP) is a potent anti-inflammatory agent. In addition to the deactivation of macrophages, dendritic cells, and microglia, VIP shifts the Th1/Th2 balance, promoting the preferential differentiation and survival of Th2 cells, to the detriment of the proinflammatory Th1 effectors. Several mechanisms operate in the Th1/Th2 shift induced by VIP. Here we report on a novel mechanism for the effect of VIP on T cell differentiation, and show that VIP inhibits Th1 differentiation by interfering directly with the IL-12 Jak2/STAT4 signaling pathway in T cells. The effect of VIP is cAMP-dependent, and appears to be mediated through the activation of protein tyrosine phosphatases (PTP), with SHP-2 as a potential target. The activation of PTPs represents a novel cAMP-downstream target for the immunomodulatory effects of VIP.