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Neuropeptide signaling through neurokinin-1 and neurokinin-2 receptors augments antigen presentation by human dendritic cells

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Title: Neuropeptide signaling through neurokinin-1 and neurokinin-2 receptors augments antigen presentation by human dendritic cells
Authors: Ohtake, Junya Browse this author
Kaneumi, Shun Browse this author
Tanino, Mishie Browse this author →KAKEN DB
Kishikawa, Takuto Browse this author
Terada, Satoshi Browse this author
Sumida, Kentaro Browse this author
Masuko, Kazutaka Browse this author
Ohno, Yosuke Browse this author
Kita, Toshiyuki Browse this author
Iwabuchi, Sadahiro Browse this author
Shinohara, Toshiya Browse this author
Tanino, Yoshinori Browse this author
Takemura, Tamiko Browse this author
Tanaka, Shinya Browse this author →KAKEN DB
Kobayashi, Hiroya Browse this author
Kitamura, Hidemitsu Browse this author →KAKEN DB
Keywords: antigen presentation
dendritic cells
hypersensitivity pneumonitis
type-1 interferon
neurokinin A
neurokinin-2 receptor
substance P
neurokinin-1 receptor
severe asthma
Issue Date: Dec-2015
Publisher: Elsevier
Journal Title: Journal of Allergy and Clinical Immunology
Volume: 136
Issue: 6
Start Page: 1690
End Page: 1694
Publisher DOI: 10.1016/j.jaci.2015.06.050
PMID: 26371842
Abstract: Background: Neurotransmitters, including substance P (SP) and neurokinin A (NKA), are widely distributed in both the central and peripheral nervous system and their receptors, neurokinin-1 receptor (NK1R) and neurokinin-2 receptor (NK2R), are expressed on immune cells. However, the role of the NKA-NK2R axis in immune responses relative to the SP-NK1R signaling cascade has not been elucidated. Objective: We sought to examine the effect of neuropeptide signaling through NK1Rand NK2R on antigen presentation by dendritic cells (DCs) and the subsequent activation of effector Th cells. Methods: Expression levels of NK1R, NK2R, HLA-class II and costimulatory molecules of human MoDCs and cytokine production by birch pollen antigen-specific CD4+ T cells cocultured with MoDCs in the presence of NK1R and NK2R antagonists were evaluated by quantitative RT-PCR, flow cytometry or ELISA. NK1R and NK2R expression in the lung of patients with asthma and hypersensitivity pneumonitis was evaluated by immunohistochemistry. Results: Human MoDCs significantly upregulated NK2R and NK1R expression in response to poly I:C stimulation in a STAT1-dependent manner. Both NK2R and NK1R were expressed on alveolar macrophages and lung DCs from patients with asthma and pneumonitis hypersensitivity. Surface expression levels of HLA-class II and costimulatory molecules on DCs were modulated by NK1R or NK2R antagonists. Activation of birch pollen-derived antigen-specific CD4+ T cells and their production of cytokines including IL-4 and IFN-γ as well as IL-12 production by MoDCs, were suppressed by blocking NK1R or NK2R after in vitro antigen stimulation. Conclusions: NK1R- and NK2R-mediated neuropeptide signaling promotes both innate and acquired immune responses through activation of human DCs.
Rights: © 2015. This manuscript version is made available under the CC-BY-NC-ND 4.0 license
Type: article (author version)
Appears in Collections:遺伝子病制御研究所 (Institute for Genetic Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 北村 秀光

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