Neurokinin-1 receptor agonists bias therapeutic dendritic cells to induce type 1 immunity by licensing host dendritic cells to produce IL-12

Brian M. Janelsins, Tina L. Sumpter, Olga A. Tkacheva, Darling M. Rojas-Canales, Geza Erdos, Alicia R. Mathers, William J. Shufesky, Walter J. Storkus, Louis D. Falo, Adrian E. Morelli, Adriana T. Larregina

Research output: Contribution to journalArticlepeer-review

27 Citations (Scopus)

Abstract

Substance-P and hemokinin-1 are proinflammatory neuropeptides with potential to promote type 1 immunity through agonistic binding to neurokinin-1 receptor (NK1R). Dendritic cells (DCs) are professional antigen-presenting cells that initiate and regulate the outcome of innate and adaptive immune responses. Immunostimulatory DCs are highly desired for the development of positive immunization techniques. DCs express functional NK1R; however, regardless of their potential DC-stimulatory function, the ability of NK1R agonists to promote immunostimulatory DCs remains unexplored. Here, we demonstrate that NK1R signaling activates therapeutic DCs capable of biasing type 1 immunity by inhibition of interleukin-10 (IL-10) synthesis and secretion, without affecting their low levels of IL-12 production. The potent type 1 effector immune response observed following cutaneous administration of NK1R-signaled DCs required their homing in skin-draining lymph nodes (sDLNs)where they induced inflammation and licensed endogenous-conventional sDLN-resident and -recruited inflammatory DCs to secrete IL-12. Our data demonstrate that NK1R signaling promotes immunostimulatory DCs, and provide relevant insight into the mechanisms used by neuromediators to regulate innate and adaptive immune responses.

Original languageEnglish
Pages (from-to)2923-2933
Number of pages11
JournalBlood
Volume121
Issue number15
DOIs
Publication statusPublished - 11 Apr 2013
Externally publishedYes

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