A bidirectional cross-talk is established between the nervous and immune systems through
common mediators including neuropeptides, neurotransmitters, and cytokines. Among
these, PACAP and VIP are two highly related neuropeptides widely distributed in the
organism with purported immunomodulatory actions. Due to their well-known anti-inflammatory
properties, administration of these peptides has proven to be beneficial in models
of acute and chronic inflammatory diseases. Nevertheless, the relevance of the endogenous
source of these peptides in the modulation of immune responses remains to be elucidated.
The development of transgenic mice with specific deletions in the genes coding for
these neuropeptides (Vip and Adcyap1) or for their G-protein-coupled receptors VPAC1,
VPAC2, and PAC1 (Vipr1, Vipr2, Adcyap1r1) has allowed to address this question, underscoring
the complexity of the immunoregulatory properties of PACAP and VIP. The goal of this
review is to integrate the existing information on the immune phenotypes of mice deficient
for PACAP, VIP, or their receptors, to provide a global view on the roles of these
endogenous neuropeptides during immunological health and disease.