A novel VIP signaling pathway in T cells cAMP-->protein tyrosine phosphatase (SHP-2?)-->JAK2/STAT4-->Th1 differentiation.

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.

journal_name

Peptides

journal_title

Peptides

authors

Liu L,Yen JH,Ganea D

doi

10.1016/j.peptides.2007.03.015

subject

Has Abstract

pub_date

2007-09-01 00:00:00

pages

1814-24

issue

9

eissn

0196-9781

issn

1873-5169

pii

S0196-9781(07)00107-6

journal_volume

28

pub_type

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