Circadian regulation of allergic reactions by immune cell-clocks

• Project/Area Number: 15H04864
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Collagenous pathology/Allergology
• Research Institution: University of Yamanashi
• Principal Investigator: NAKAO Atsuhito 山梨大学, 大学院総合研究部, 教授 (80317445)
• Research Collaborator: NAKAMURA Yuki ; ISHIMARU Kayoko
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000); Fiscal Year 2017: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2016: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000); Fiscal Year 2015: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
• Keywords: アレルギー / 概日時計 / 免疫細胞 / 時計遺伝子 / 免疫 / 遺伝子改変マウス

Outline of Final Research Achievements

We have established dendritic cell-selective Bmal1-deficient mice (DC-Bmal1-deficient mice) in this study.
Upon introduction of Derf1, a major mite allergen,-induced asthma model, DC-Bmal1-deficient mice showed reduced airway inflammation associated with suppression of Derf1-specific IgE antibody and T cell responses. Preliminary studies showed that migration of dendritic cells into the regional lymph nodes were suppressed in DC-Bmal1-deficient mice. These findings suggest that deficiency of Bmal1 in dendritic cells suppresses sensitization to Derf1 by inhibition migration of DC to lymph nodes. We are under investigation how the suppression of DC migration occurs in DC-Bmal1-deficient mice.

Research Products

• [Journal Article] Circadian clock-dependent increase in salivary IgA secretion modulated by sympathetic receptor activation in mice. (2017)
  • Author(s): Wada M, Orihara K, Kamagata M, Hama K, Sasaki H, Haraguchi A, Miyakawa H, Nakao A, Shibata S.
  • Journal Title: Scientific Reports Volume: ７ Issue: 1 Pages: 8802-8802
  • DOI: 10.1038/s41598-017-09438-0
  • Peer Reviewed / Open Access
• [Journal Article] The frequency of Th17 cells in the small intestine exhibits a day-night varidation dependent on circadian clock activity. (2017)
  • Author(s): Thu Le HP, Nakamura Y, Oh-Oka K, Ishimaru K, Nakajima S, Nakao A
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 490 (2) Issue: 2 Pages: 290-295
  • DOI: 10.1016/j.bbrc.2017.06.038
  • Peer Reviewed / Open Access
• [Journal Article] Induction of colonic regulatory T cells by 5-aminosalicylic acid (5-ASA) by activating the aryl hydrocarbon receptor. (2017)
  • Author(s): Oh-oka K, Kojima Y, Uchida K, Yoda M, Ishimaru K, Nakajima S, Hemmi J, Kano H, Fujii-Kuriyama Y, Katoh R, Ito H, Nakao A
  • Journal Title: Cell Mol Gastroenterol Hepatol Volume: 印刷中 Issue: 1 Pages: 135-151
  • DOI: 10.1016/j.jcmgh.2017.03.010
  • Peer Reviewed / Open Access
• [Journal Article] Regulation of plasma histamine levels by the mast cell clock and its modulation by stress. (2017)
  • Author(s): Nakamura Y, Ishimaru K, Shibata S, Nakao A.
  • Journal Title: Scientific Reports Volume: 7 Issue: 1 Pages: 39934-39934
  • DOI: 10.1038/srep39934
  • Peer Reviewed / Open Access
• [Journal Article] <i>Clock</i>-dependent temporal regulation of IL-33/ST2-mediated mast cell response (2017)
  • Author(s): Kawauchi T, Ishimaru K, Nakamura Y, Nakano N, Hara M, Ogawa H, Okumura K, Shibata S, Nakao A
  • Journal Title: Allergology International Volume: 66 Issue: 3 Pages: 472-478
  • DOI: 10.1016/j.alit.2017.02.004
  • NAID: 130005858846
  • ISSN: 1323-8930, 1440-1592
  • Peer Reviewed / Open Access
• [Journal Article] Clock Genes Regulate the Circadian Expression of Piezo1, TRPV4, Connexin26, and VNUT in an Ex Vivo Mouse Bladder Mucosa. (2017)
  • Author(s): 5.Ihara T, Mitsui T, Nakamura Y, Kira S, Nakagomi H, Sawada N, Hirayama Y, Shibata K, Shigetomi E, Shinozaki Y, Yoshiyama M, Andersson KE, Nakao A, Takeda M, Koizumi S
  • Journal Title: PLoS One Volume: 12 Issue: 1 Pages: e0168234-e0168234
  • DOI: 10.1371/journal.pone.0168234
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The efficacy of sublingual immunotherapy for allergic rhinitis may vary with the time of day. (2016)
  • Author(s): Igarashi S, Suzuki K, Nakamura Y, Ishimaru K, Fukano C, Masuyama K, Ohashi-Doi K, Nakao A
  • Journal Title: Int Arch Allergy Immunol Volume: 171 Issue: 2 Pages: 111-118
  • DOI: 10.1159/000450954
  • Peer Reviewed / Open Access
• [Journal Article] Synergistic anti-tumor effect with indoleamine 2,3-dioxygenase inhibition and temozolomide in a murine glioma model. (2016)
  • Author(s): 1.Hanihara M, Kawataki T, Oh-oka K, Mitsuka K, Nakao A, and Kinouchi H
  • Journal Title: Journal of Neurosurgery Volume: in printing Issue: 6 Pages: 1594-1601
  • DOI: 10.3171/2015.5.jns141901
  • Peer Reviewed
• [Journal Article] The Alarmin IL-33 Derived from HSV-2-Infected Keratinocytes Triggers Mast Cell-Mediated Antiviral Innate Immunity. (2016)
  • Author(s): Aoki R, Kawamura T, Goshima F, Ogawa Y, Nakae S, Moriishi K, Nakao A, Shimada S
  • Journal Title: J Invest Dermatol Volume: 印刷中 Issue: 6 Pages: 1290-1292
  • DOI: 10.1016/j.jid.2016.01.030
  • Peer Reviewed / Open Access
• [Journal Article] Establishment of a Therapeutic Anti-Pan HLA-Class II Monoclonal Antibody That Directly Induces Lymphoma Cell Death via Large Pore Formation. (2016)
  • Author(s): Matsuoka S, Ishii Y, Nakao A, Abe M, Ohtsuji N, Momose S, Jin H, Arase H, Sugimoto K, Nakauchi Y, Masutani H, Maeda M, Yagita H, Komatsu N, Hino O
  • Journal Title: PLoS One Volume: 11 Issue: 3 Pages: e0150496-e0150496
  • DOI: 10.1371/journal.pone.0150496
  • NAID: 120005838168
  • Peer Reviewed / Open Access
• [Journal Article] Synergistic antitumor effect with indoleamine 2,3-dioxygenase inhibition and temozolomide in a murine glioma model. (2016)
  • Author(s): Hanihara M, Kawataki T, Oh-oka K, Mitsuka K, Nakao A, Kinouchi H
  • Journal Title: Journal of Neurosurgery Volume: 印刷中
  • Peer Reviewed / Open Access
• [Journal Article] Inhibition of IgE-mediated allergic reactions by pharmacologically targeting the circadian clock. (2015)
  • Author(s): Nakamura Y, Nakano N, Ishimaru K, Ando N, Katoh R, Suzuki-Inoue K, Koyanagki S, Ogawa H, Okumura K, Shibata S, Nakao A
  • Journal Title: The Journal of allergy and clinical immunology Volume: 137(4) Issue: 4 Pages: 1226-1235
  • DOI: 10.1016/j.jaci.2015.08.052
  • Peer Reviewed / Open Access
• [Journal Article] Antigen exposure in the late light period induces severe symptoms of food allergy in an OVA-allergic mouse model. (2015)
  • Author(s): Tanabe K, Kitagawa E, Wada M, Haraguchi A, Orihara K, Tahara Y, Nakao A, Shibata S.
  • Journal Title: Sci Rep. Volume: 5 Issue: 1 Pages: 14424-14424
  • DOI: 10.1038/srep14424
  • Peer Reviewed / Open Access
• [Journal Article] Circadian Gene Clock Regulates Psoriasis-Like Skin Inflammation in Mice. (2015)
  • Author(s): Ando N, Nakamura Y, Aoki R, Ishimaru K, Ogawa H, Okumura K, Shibata S, Shimada S, Nakao A
  • Journal Title: J Invest Dermatol Volume: 135 Issue: 12 Pages: 3001-3008
  • DOI: 10.1038/jid.2015.316
  • Peer Reviewed / Open Access
• [Journal Article] IL-7: AhR We Ready for a New Cytokine to Fight Colitis? (2015)
  • Author(s): Nakao A
  • Journal Title: Dig Dis Sci Volume: 60 Issue: 7 Pages: 1876-1877
  • DOI: 10.1007/s10620-015-3721-x
  • Peer Reviewed / Open Access
• [Journal Article] Positive association between serum thymic stromal lymphopoietin and anti-citrullinated peptide antibodies in patients with rheumatoid arthritis. (2015)
  • Author(s): Koyama K, Ohba T, Haro H, Nakao A
  • Journal Title: Clin Exp Immunol Volume: 181 Issue: 2 Pages: 239-243
  • DOI: 10.1111/cei.12632
  • Peer Reviewed / Open Access
• [Journal Article] The Cricadian Clock Functions As A Potent Regulator of Allergic Reaction. [Review] (2015)
  • Author(s): Nakao A, Nakamura Y, Shibata S
  • Journal Title: Allergy Volume: 70(5) Issue: 5 Pages: 467-473
  • DOI: 10.1111/all.12596
  • Peer Reviewed / Open Access
• [Presentation] Inhibition of IgE-mediated allergic reaction by pharmacologically targeting the circadian clock. (2016)
  • Author(s): Nakamura Y, Nakao A, Shibata S
  • Organizer: 第45回日本免疫学会学術集会
  • Place of Presentation: 沖縄コンベンションセンター（沖縄県宜野湾市）
  • Year and Date: 2016-12-05
• [Presentation] 5-amino salicylic acid (5-ASA) induces the colonic regulatory Tcells via the activation of the aryl hydrocarbon receptor signaling pathway. (2016)
  • Author(s): Oh-oka K, Nakao A
  • Organizer: 第45回日本免疫学会学術集会
  • Place of Presentation: 沖縄コンベンションセンター（沖縄県宜野湾市）
  • Year and Date: 2016-12-05
• [Presentation] Migration of Th17 cells to the small intestine is temporally regulated by the circadian clock. (2016)
  • Author(s): Le Pham Thu Ha, Nakamura Y, Nakao A
  • Organizer: 第45回日本免疫学会学術集会
  • Place of Presentation: 沖縄コンベンションセンター（沖縄県宜野湾市）
  • Year and Date: 2016-12-05
• [Presentation] Regulation of plasma histamine levels by the mast cell clock and its modulation by stress. (2016)
  • Author(s): 中村勇規,柴田重信,中尾篤人
  • Organizer: 第23回日本時間生物学会学術大会
  • Place of Presentation: 名古屋大学豊田講堂（愛知県名古屋市）
  • Year and Date: 2016-11-12
• [Presentation] AHR activation by probiotics inhibits colitis. (2016)
  • Author(s): Nakao A
  • Organizer: AHR 2016 The aryl hydrocarbon receptor as a central mediator of health and disease
  • Place of Presentation: New York（USA）
  • Year and Date: 2016-08-03
  • Int'l Joint Research / Invited
• [Presentation] 薬理学的概日時計制御によるIgE依存性アレルギー反応の抑制. (2016)
  • Author(s): 中村勇規,柴田重,中尾篤人
  • Organizer: 第65回日本アレルギー学会学術大会
  • Place of Presentation: 東京国際フォーラム（東京都千代田区）
  • Year and Date: 2016-06-17
• [Presentation] Circadian Regulation of Allergic Reaction. (2016)
  • Author(s): Nakao A
  • Organizer: 2016 SRBR Meeting
  • Place of Presentation: Florida（USA）
  • Year and Date: 2016-05-21
  • Int'l Joint Research / Invited
• [Presentation] The mast cell-clock regulates blood histamine levels: implication for stress-induced exacerbation of allergy. (2016)
  • Author(s): Nakao A
  • Organizer: 31th symposium of the Collegium Internationale Allergologicum
  • Place of Presentation: Charleston（USA）
  • Year and Date: 2016-04-03
• [Presentation] The mast cell-clock regulates blood histamine levels: implication for stress-induced exacerbation of allergy. (2016)
  • Author(s): Nakao A
  • Organizer: 31th symposium of the Collegium Internationale Allergologicum
  • Place of Presentation: Charleston, USA
  • Year and Date: 2016-04-03
  • Int'l Joint Research / Invited
• [Presentation] Inhibition of IgE-Mediated Allergic Reaction By Pharmacologically Targeting the Circadian Clock. (2016)
  • Author(s): Nakamura Y, Shibata S, Nakao A
  • Organizer: 2016 AAAAI Annual Meeting
  • Place of Presentation: Los Angeles, USA
  • Year and Date: 2016-03-04
  • Int'l Joint Research
• [Presentation] Allergy:From Bench to Bedside and Beyond. (2015)
  • Author(s): Nakao A
  • Organizer: 第44回日本免疫学会学術集会
  • Place of Presentation: 札幌コンベンションセンター（北海道札幌市）
  • Year and Date: 2015-11-18
  • Invited
• [Presentation] スギ花粉症患者好塩基球のスギ花粉に対する反応性の日内変動 (2015)
  • Author(s): 安藤典子,中村勇規,石丸かよ子,島田眞路,中尾篤人
  • Organizer: 第64回日本アレルギー学会学術大会
  • Place of Presentation: グランドプリンスホテル新高輪（東京都港区）
  • Year and Date: 2015-05-26
• [Presentation] IL-33依存性マスト細胞応答は時計遺伝子Clockにより制御される (2015)
  • Author(s): 河内貴広,中村勇規,中尾篤人
  • Organizer: 第64回日本アレルギー学会学術大会
  • Place of Presentation: グランドプリンスホテル新高輪（東京都港区）
  • Year and Date: 2015-05-26
• [Presentation] レスベラトロール二量体であるε-ビニフェリンによるIgE依存性アレルギー反応の抑制効果 (2015)
  • Author(s): 齋藤一歩,大岡杏子,久本雅嗣，奥田徹,中尾篤人
  • Organizer: 第64回日本アレルギー学会学術大会
  • Place of Presentation: グランドプリンスホテル新高輪（東京都港区）
  • Year and Date: 2015-05-26
• [Book] アバス-リックマン-ピレ 分子細胞免疫学 原著第9版 (2017)
  • Author(s): 中尾篤人
  • Total Pages: 577
  • Publisher: エルゼビア・ジャパン株式会社
• [Remarks] 山梨大学医学部免疫学講座ホームページ
  • URL: http://www.med.yamanashi.ac.jp/clinical_basic/para0imm/kenkyuu/kenkyuu.php