Opposing impacts of anti-inflammatory vs proinflammatory neuropeptides on DCs. VIP, α-MSH, and CGRP downregulate expression of costimulatory molecules and production of inflammatory cytokines and IL-12 by DCs, whereas augmenting their production of IL-10. The resulting tolerogenic DCs, in turn, induce immunologic tolerance by favoring Th2-biased immunity and promoting Treg generation. By contrast, SP and hemokinin-1 elevate expression of MHC class II molecule, costimulatory molecules, adhesion molecules, and CCR7 on DCs. Not only do the DCs stimulated with NK1R agonists migrate to draining lymph nodes (LNs), but they also induce recruitment of Ly6C⁺ inflammatory DCs to the same LNs, where they physically interact with and trigger IL-12 production by inflammatory DCs. Thus, NKR1 agonists promote Th1-polarized immunity through indirectly activating inflammatory DCs. Professional illustration by Paulette Dennis.