| 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 |
| neuropeptide |
| STAT1 |
| 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 http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/67660 |
| 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)
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