Neurokinin A reduces the influx of inflammatory cells into the skin in a mast-cell dependent manner

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Presentation Time: 10:15 AM - 10:30 AM
Abstract ID: 5497 - B

Presenting Author:
Joharis Barreto , Undergraduate Researcher at Univ. of Pittsburgh Sch. of Med.

Abstract:

Cutaneous mast cells promote immune responses but are also involved in reducing inflammation and in promoting immune resolution. Mechanisms initiating the anti-inflammatory function of mast cells are poorly defined. Mast cells reside in close proximity to neurons and their activation is modulated by neuropeptides, including the tachykinin family members. Neurokinin A (NKA) is an understudied tachykinin family member that limits cutaneous inflammation in a murine contact hypersensitivity (CHS) model but increases inflammation in colitis. In this study, the regulatory function of NKA in cutaneous inflammation is mechanistically evaluated using a robust model of DNFB-induced CHS. Administration of NKA prior to sensitization inhibited the expression of inflammatory cytokines and chemokines, including Il1b, Il6 and Ccl2. Correspondingly, NKA reduced recruitment of CCR2⁺ neutrophils and inflammatory monocytes to the skin. In mast cell-deficient Mcpt5Cre⁺ x Rosa26DTA and in mice in which mast cells do not produce IL-10 (Mcpt5Cre⁺ x Il10^fl/fl) the capacity for NKA to reduce cytokines and chemokines was diminished. Lastly, in skin explant NKA diminished IL-1b and CCL2, genes upregulated after DNFB-treatment. Collectively, these data suggest that NKA reduces inflammation in the skin in a mast cell/IL-10 dependent manner and demonstrate  a novel regulatory pathway for NKA in the skin that acts on mast cells to unleash their potential to reduce cutaneous inflammation.