A novel VIP signaling pathway in T cells cAMP-->protein tyrosine phosphatase (SHP-2?)-->JAK2/STAT4-->Th1 differentiation.
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.
Liu
Li
L
Rutgers University, Department of Biological Sciences, 101 Warren St., Newark, NJ 07102, USA.
Yen
Jui-Hung
JH
Ganea
Doina
D
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D000242:Cyclic AMP / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D005434:Flow Cytometry; D018664:Interleukin-12 / Q000494:pharmacology; D053614:Janus Kinase 2 / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D051379:Mice; D008954:Models, Biological; D010766:Phosphorylation / Q000187:drug effects; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D050797:STAT4 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction; D018417:Th1 Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
D050797:STAT4 Transcription Factor; D018664:Interleukin-12; D014660:Vasoactive Intestinal Peptide; D000242:Cyclic AMP; D053614:Janus Kinase 2; D017868:Cyclic AMP-Dependent Protein Kinases; D017027:Protein Tyrosine Phosphatases