VIP/PACAP preferentially attract Th2 effectors through differential regulation of chemokine production by dendritic cells

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
M DelgadoD Ganea

Abstract

The neuropeptides vasoactive intestinal peptide (VIP) and the structurally related pituitary adenylate cyclase-activating polypeptide (PACAP) are potent immunomodulatory agents, acting as general anti-inflammatory factors. VIP, produced and secreted by Th2 cells following antigen stimulation, participates in a Th2 autoregulatory loop, promoting Th2-type responses through several nonexcluding mechanisms. VIP and PACAP affect the differentiation of CD4+ T cells directly and indirectly through antigen-presenting cells and promote the proliferation and/or survival of the Th2 effectors. Th1 and Th2 effectors express different chemokine receptors that control migration in response to various chemokines. In this study, we investigated the effects of VIP/PACAP on the production of CXCL10 (a Th1 chemokine) and of CCL22 (a Th2 chemokine) by bone marrow-derived dendritic cells. We found that VIP and PACAP inhibit CXCL10, while promoting CCL22 production, and that the effects are mediated through the VPAC1 receptor and involve cAMP/PKA as intracellular messengers. The induction of CCL22 and the suppression of CXCL10 in VIP/PACAP-treated dendritic cells results in the preferential chemoattraction of Th2 effectors both in vivo and in vitro. ...Continue Reading

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Citations

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