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Published on: September 28, 2018
A novel VIP signaling pathway in T cells cAMP-->protein tyrosine phosphatase (SHP-2?)-->JAK2/STAT4-->Th1
Li Liu1, Jui-Hung Yen, Doina Ganea
1Rutgers University, Department of Biological Sciences, 101 Warren St., Newark, NJ 07102, USA.
Abstract:
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-12Jak2/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.
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