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- W4313385592 abstract "Abstract Mast cells (MCs) are potent effector cells in atopic diseases, like asthma and atopic dermatitis. In the skin, MCs reside in the dermis, in close proximity to sensory nerves. In this shared geographical space, MCs and neurons may have evolved common mechanisms for responding to noxious stimuli and for maintaining homeostasis, including responsiveness to neuropeptides. Sensory nerves release neuropeptides with immune functions including the tachykinin family member, neurokinin A (NKA). Recent studies highlight immune functions for NKA but a role for NKA in MC biology has not been explored. NKA signals with high affinity through the neurokinin 2 receptor (NK2R) that has been reported to be anti-inflammatory in the skin. In the current study, we hypothesized that NKA would dampen MC activation initiated by FcɛRI. Our data demonstrated that, in vitro, mouse bone marrow (BM) derived MCs expressed low levels of the NK2R, which was upregulated following FcɛRI activation and maintained by STAT3 signaling. The addition of NKA to MC cultures downregulated surface expression of the prototypical MC markers, FcɛRIα and c-Kit. This effect was overcome with IgE and cross-linking antigen (Ag). NKA alone did not affect degranulation or cytokine release. But, NKA increased the percentage of MCs releasing granules in response to IgE + Ag, while decreasing the secretion of IL-4, IL-13 and IL-6 in response to IgE + Ag. In vivo, intradermal administration of NKA reduced IgE-dependent MC functions in a murine model of passive cutaneous anaphylaxis. Our data suggest that NKA reduces the inflammatory capacity of MCs and that activation of the NKA/NK2R axis has a therapeutic potential for MC mediated atopic diseases." @default.
- W4313385592 created "2023-01-06" @default.
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- W4313385592 date "2016-05-01" @default.
- W4313385592 modified "2023-10-14" @default.
- W4313385592 title "Neurokinin A reduces FcɛRI-triggered inflammation mediated by cutaneous mast cells." @default.
- W4313385592 doi "https://doi.org/10.4049/jimmunol.196.supp.123.10" @default.
- W4313385592 hasPublicationYear "2016" @default.
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