Details of a Researcher - Moriwaki, Yasuhiro

Moriwaki, Yasuhiro

写真a

Affiliation: Faculty of Pharmacy, Department of Pharmacy 薬学教育研究センター（Shiba-Kyoritsu）

Position: Assistant Professor/Senior Assistant Professor

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Career 【 Display / hide 】

2002.04

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2003.03

大阪府立成人病センター研究所, 日本学術振興会特別研究員
2003.04

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2003.08

理化学研究所　脳科学総合研究センター, 日本学術振興会特別研究員
2003.09

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2005.03

理化学研究所　脳科学総合研究センター, 研究員
2005.04

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2007.03

共立薬科大学, 助手
2007.04

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2008.03

共立薬科大学, 助教

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Academic Background 【 Display / hide 】

2000.04

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2003.03

Nara Institute of Science and Technology, Graduate School, Division of Biological Science

Graduate School, Completed, Doctoral course

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Academic Degrees 【 Display / hide 】

博士（バイオサイエンス）, 奈良先端科学技術大学院大学, Coursework, 2003.03

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Licenses and Qualifications 【 Display / hide 】

第一種放射線取扱主任者（選任）, 2022.04

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Papers 【 Display / hide 】

Regulation of immune functions by non-neuronal acetylcholine (ACh) via muscarinic and nicotinic ACh receptors.

Mashimo M, Moriwaki Y, Misawa H, Kawashima K, Fujii T.

International Journal of Molecular Sciences （MDPI) 22 （ 13 ） 6818 2021.06

Research paper (scientific journal), Joint Work, Accepted, ISSN 16616596

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Acetylcholine (ACh) is the classical neurotransmitter in the cholinergic nervous system. However, ACh is now known to regulate various immune cell functions. In fact, T cells, B cells, and macrophages all express components of the cholinergic system, including ACh, muscarinic, and nicotinic ACh receptors (mAChRs and nAChRs), choline acetyltransferase, acetylcholinesterase, and choline transporters. In this review, we will discuss the actions of ACh in the immune system. We will first briefly describe the mechanisms by which ACh is stored in and released from immune cells. We will then address Ca2+ signaling pathways activated via mAChRs and nAChRs on T cells and B cells, highlighting the importance of ACh for the function of T cells, B cells, and macrophages, as well as its impact on innate and acquired (cellular and humoral) immunity. Lastly, we will discuss the effects of two peptide ligands, secreted lymphocyte antigen-6/urokinase-type plasminogen activator receptor-related peptide-1 (SLURP-1) and hippocampal cholinergic neurostimulating peptide (HCNP), on cholinergic activity in T cells. Overall, we stress the fact that ACh does not function only as a neurotransmitter; it impacts immunity by exerting diverse effects on immune cells via mAChRs and nAChRs.
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New pathways for the skin´s stress response: the cholinergic neuropeptide SLURP-1 can activate mast cells and alter cytokine production in mice.

Ertle CM, Rommel FR, Tumala S, Moriwaki Y, Klein J, Kruse J, Gieler U, Peters EMJ.

Frontiers in Immunology （Frontiers in Immunology) 12 631881 2021.03

Research paper (scientific journal), Joint Work, Accepted

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Background: The alpha7 nicotinic acetylcholine receptor (Chrna7) plays an essential anti-inflammatory role in immune homeostasis and was recently found on mast cells (MC). Psychosocial stress can trigger MC hyperactivation and increases pro-inflammatory cytokines in target tissues such as the skin. If the cholinergic system (CS) and Chrna7 ligands play a role in these cascades is largely unknown. Objective: To elucidate the role of the CS in the response to psychosocial stress using a mouse-model for stress-triggered cutaneous inflammatory circuits. Methods: Key CS markers (ACh, Ch, SLURP-1, SLURP-2, Lynx1, Chrm3, Chrna7, Chrna9, ChAT, VAChT, Oct3, AChE, and BChE) in skin and its MC (sMC), MC activation, immune parameters (TNFα, IL1β, IL10, TGFβ, HIF1α, and STAT3) and oxidative stress were analyzed in skin from 24 h noise-stressed mice and in cultured MC (cMC) from C57BL/6 or Chrna7-Knockout mice. Results: First, Chrna7 and SLURP-1 mRNA were exclusively upregulated in stressed skin. Second, histomorphometry located Chrna7 and SLURP-1 in nerves and sMC and demonstrated upregulated contacts and increased Chrna7+ sMC in stressed skin, while 5 ng/mL SLURP-1 degranulated cMC. Third, IL1β+ sMC were high in stressed skin, and while SLURP-1 alone had no significant effect on cMC cytokines, it upregulated IL1β in cMC from Chrna7-KO and in IL1β-treated wildtype cMC. In addition, HIF1α+ sMC were high in stressed skin and Chrna7-agonist AR-R 17779 induced ROS in cMC while SLURP-1 upregulated TNFα and IL1β in cMC when HIF1α was blocked. Conclusions: These data infer that the CS plays a role in the regulation of stress-sensitive inflammatory responses but may have a surprising pro-inflammatory effect in healthy skin, driving IL1β expression if SLURP-1 is involved.
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Endogenous neurotoxin-like protein Ly6H inhibits alpha7 nicotinic acetylcholine receptor currents at the plasma membrane.

Moriwaki Y*, Kubo N, Watanabe M, Asano S, Shinoda T, Sugino T, Ichikawa D, Tsuji S, Kato F, Misawa H.

Scientific Reports （Scientific Reports) 10 （ 1 ） 11996 2020.07

Research paper (scientific journal), Joint Work, Accepted

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© 2020, The Author(s). α7 nicotinic acetylcholine receptors (nAChRs) are widely expressed in the central nervous system and regarded as potential therapeutic targets for neurodegenerative conditions, such as Alzheimer’s disease and schizophrenia. Yet, despite the assumed pathophysiological importance of the α7 nAChR, molecular physiological characterization remains poorly advanced because α7 nAChR cannot be properly folded and sorted to the plasma membranes in most mammalian cell lines, thus preventing the analyses in heterologous expression system. Recently, ER-resident membrane protein NACHO was discovered as a strong chaperone for the functional expression of α7 nAChR in non-permissive cells. Ly6H, a brain-enriched GPI-anchored neurotoxin-like protein, was reported as a novel modulator regulating intracellular trafficking of α7 nAChR. In this study, we established cell lines that stably and robustly express surface α7 nAChR by introducing α7 nAChR, Ric-3, and NACHO cDNA into HEK293 cells (Triple α7 nAChR/RIC-3/NACHO cells; TARO cells), and re-evaluated the function of Ly6H. We report here that Ly6H binds with α7 nAChRs on the cell membrane and modulates the channel activity without affecting intracellular trafficking of α7 nAChR.
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Minireview: Divergent roles of α7 nicotinic acetylcholine receptors expressed on antigen-presenting cells and CD4<sup>+</sup> T cells in the regulation of T cell differentiation

Mashimo M., Fujii T., Ono S., Moriwaki Y., Misawa H., Kawashima K.

International Immunopharmacology （International Immunopharmacology) 82 106306 2020.02

Research paper (scientific journal), Accepted, ISSN 15675769

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© 2020 Elsevier B.V. α7 nAChRs expressed on immune cells regulate antigen-specific antibody and proinflammatory cytokine production. Using spleen cells from ovalbumin (OVA)-specific T cell receptor transgenic DO11.10 mice and the α7 nAChR agonist GTS-21, investigation of (1) antigen processing-dependent and (2) -independent, antigen presenting cell (APC)-dependent, naïve CD4+ T cell differentiation, as well as (3) non-specific APC-independent, anti-CD3/CD28 mAbs-induced CD4+ T cell differentiation, revealed the differential roles of α7 nAChRs expressed on T cells and APCs in the regulation of CD4+ T cell differentiation. GTS-21 suppressed OVA-induced antigen processing- and APC-dependent differentiation into regulatory T cells (Tregs) and effector T cells (Th1, Th2 and Th17) without affecting OVA uptake or cell viability. By contrast, GTS-21 upregulated OVA peptide-induced antigen processing-independent T cell differentiation into all lineages. During anti-CD3/CD28 mAbs-induced T cell differentiation in the presence of polarizing cytokines, GTS-21 promoted wild-type T cell differentiation into all lineages, but did not affect α7 nAChR-deficient T cell differentiation. These results demonstrate (1) that α7 nAChRs on APCs downregulate T cell differentiation by inhibiting antigen processing and thereby interfering with antigen presentation; and (2) that α7 nAChRs on T cells upregulate differentiation into Tregs and effector T cells. Thus, the divergent roles of α7 nAChRs on APCs and T cells likely regulate the intensity of immune responses. These findings suggest the possibility of using α7 nAChR agonists to harvest greater numbers of Tregs and Th1 and Th2 cells for adoptive immune therapies for treatment of autoimmune diseases and cancers.
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Distinct roles of α7 nAChRs in antigen-presenting cells and CD4<sup>+</sup> T cells in the regulation of T cell differentiation

Mashimo M., Komori M., Matsui Y., Murase M., Fujii T., Takeshima S., Okuyama H., Ono S., Moriwaki Y., Misawa H., Kawashima K.

Frontiers in Immunology （Frontiers in Immunology) 10 （ MAY ） 1102 2019.05

Research paper (scientific journal), Joint Work, Accepted

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Copyright © 2019 Mashimo, Komori, Matsui, Murase, Fujii, Takeshima, Okuyama, Ono, Moriwaki, Misawa and Kawashima. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. It is now apparent that immune cells express a functional cholinergic system and that α7 nicotinic acetylcholine receptors (α7 nAChRs) are involved in regulating T cell differentiation and the synthesis of antigen-specific antibodies and proinflammatory cytokines. Here, we investigated the specific function α7 nAChRs on T cells and antigen presenting cells (APCs) by testing the effect of GTS-21, a selective α7 nAChR agonist, on differentiation of CD4+ T cells from ovalbumin (OVA)-specific TCR transgenic DO11.10 mice activated with OVA or OVA peptide323−339 (OVAp). GTS-21 suppressed OVA-induced antigen processing-dependent development of CD4+ regulatory T cells (Tregs) and effector T cells (Th1, Th2, and Th17). By contrast, GTS-21 up-regulated OVAp-induced antigen processing-independent development of CD4+ Tregs and effector T cells. GTS-21 also suppressed production of IL-2, IFN-γ, IL-4, IL-17, and IL-6 during OVA-induced activation but, with the exception IL-2, enhanced their production during OVAp-induced activation. In addition, during antigen-nonspecific, APC-independent anti-CD3/CD28 antibody-induced CD4+ polyclonal T cell activation in the presence of respective polarizing cytokines, GTS-21 promoted development of all lineages, which indicates that GTS-21 also acts via α7 nAChRs on T cells. These results suggest 1) that α7 nAChRs on APCs suppress CD4+ T cell activation by interfering with antigen presentation through inhibition of antigen processing; 2) that α7 nAChRs on CD4+ T cells up-regulate development of Tregs and effector T cells; and that α7 nAChR agonists and antagonists could be potentially useful agents for immune response modulation and enhancement.
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Papers, etc., Registered in KOARA 【 Display / hide 】

Development of novel therapeutic strategies for myasthenia gravis

Moriwaki, Yasuhiro

福澤諭吉記念慶應義塾学事振興基金事業報告集（福澤基金運営委員会) 2020
Elucidation of the molecular mechanism of HEG1 in controlling proliferation of mesothelioma cell.

Moriwaki, Yasuhiro

学事振興資金研究成果実績報告書（慶應義塾大学) 2019
A novel therapeutic strategy against psoriasis by using nicotinic acetylcholine receptor modulator, SLURP-1

Moriwaki, Yasuhiro

科学研究費補助金研究成果報告書 2016

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Reviews, Commentaries, etc. 【 Display / hide 】

ニコチン受容体修飾因子SLURP-1による乾癬の新規治療戦略

森脇康博

臨床免疫・アレルギー科 66 ( 1 ) 45 - 49 2016.07

Article, review, commentary, editorial, etc. (trade magazine, newspaper, online media), Single Work
パーキンソン病と小胞体ストレス

森脇康博, 高橋良輔

現代医療 36 ( 4 ) 129 - 134 2004.04

Article, review, commentary, editorial, etc. (trade magazine, newspaper, online media), Joint Work

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Presentations 【 Display / hide 】

コーヒーによる神経炎症の抑制分子メカニズムの解析

村田大典, 森脇康博, 多胡憲治,中澤洋介, 田村悦臣, 多胡めぐみ.

第95回日本生化学会大会 (名古屋) ,

2022.11
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Poster presentation
コーヒー及び含有成分ピロカテコールによる神経炎症の抑制効果

村田大典, 森脇康博, 多胡憲治,中澤洋介, 田村悦臣, 多胡めぐみ.

第66回日本薬学会関東支部大会 (神奈川) ,

2022.09
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Oral presentation (general)
内在性神経毒類似タンパク質によるニコチン受容体の機能変換メカニズムの解明

森脇康博, 三澤日出巳.

第36回令和3年度喫煙科学研究財団助成研究発表会 (東京) ,

2022.07
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Oral presentation (general)
コーヒーによる神経炎症の抑制効果

村田大典, 森脇康博, 多胡憲治,中澤洋介, 田村悦臣, 多胡めぐみ

第65回日本薬学会関東支部大会 (千葉) ,

2021.09
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Oral presentation (general)
コーヒーによる神経炎症の抑制分子メカニズムの解析.

村田大典, 森脇康博, 多胡憲治,中澤洋介, 田村悦臣, 多胡めぐみ.

2021年度日本生化学会関東支部例会 (群馬) ,

2021.06
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Oral presentation (general)

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Research Projects of Competitive Funds, etc. 【 Display / hide 】

重症筋無力症に対する二重特異性抗体薬を用いた根治治療法の開発

2020.04

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2023.03

文部科学省・日本学術振興会, 科学研究費助成事業, 基盤研究(C), Research grant, Principal investigator
新しい糖鎖創薬の標的・HEG1に対する抗体医薬の開発

2018.11

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2021.03

国立研究開発法人日本医療研究開発機構(AMED), 次世代治療・診断実現のための創薬基盤技術開発事業, No Setting
内在性神経毒類似タンパク質によるニコチン受容体調節の生理的役割の解明

2016.04

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2021.03

喫煙科学研究財団, No Setting
内因性nAChR活性化蛋白質SLURP-1のT細胞分化に及ぼす作用の薬学的研究

2015.04

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2018.03

文部科学省・日本学術振興会, 基盤研究(C), No Setting
A novel therapeutic strategy against psoriasis by using nicotinic acetylcholine receptor modulator, SLURP-1

2015.04

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2017.03

MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Young Scientists (B), Principal investigator

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SLURP1 is the causal gene for Mal de Meleda (MDM), an autosomal recessive skin disorder　characterized by diffuse palmoplantar keratoderma and transgressive keratosis. Recently, SLURP1-deficient mice show MDM-like symptoms such as severe palmoplantar keratoderma characterized by increased keratinocyte proliferation and water barrier defects. Although SLURP1 likely serves as an important proliferation/differentiation factor in keratinocytes, the possible relation between SLURP1 and other skin diseases, such as psoriasis and atopic dermatitis, has not been studied. In our experiment, we found SLURP1 expression is greatly increased within the skin lesions in a psoriatic mouse model. In addition, recombinant SLURP1 suppressed the growth of S. aureus, which is associated with disease severity in psoriasis. These results suggest that SLURP1 may contribute to the pathogenesis of psoriasis.

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Awards 【 Display / hide 】

第137回日本薬理学会関東部会　若手優秀発表賞

渡邉みずほ, 森脇康博, 久保那月, 加藤総夫, 三澤日出巳., 2017.10, 内在性神経毒素類似タンパク質Ly6Hによるニコチン受容体調整.

Type of Award： Award from Japanese society, conference, symposium, etc.
第131回日本薬理学会関東部会　若手優秀発表賞

森﨑祐太, 坪田充司, 森脇康博, 山中宏二, 三澤日出巳., 2014.10, 筋萎縮性側索硬化症における運動ニューロン変性とオステオポンチン及びマトリックスメタロプロテアーゼ-9の関連の検討.

Type of Award： Award from Japanese society, conference, symposium, etc.