Elucidation of the regulatory mechanism of allergic disease via commensal microbiota and regulatory T cells

• Project/Area Number: 16H05350
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pediatrics
• Research Institution: University of Tsukuba
• Principal Investigator: Nakahashi-Oda Chigusa 筑波大学, 医学医療系, 助教 (50510054)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000); Fiscal Year 2018: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2017: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2016: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
• Keywords: エクソソーム / アレルギー / CD300a / 制御性T細胞 / アレルギー疾患 / 常在菌 / ケラチノサイト / アポトーシス細胞 / ホスファチジルセリン / 免疫学

Outline of Final Research Achievements

Epithelial tissue including skin, airway and gastrointestinal tract serves as the habitat of commensal microbiota and also the site of allergic diseases. We have elucidated that the regulation of regulatory T cells (Treg cells) which is the cell population that able to suppress the inflammation, by commensal microbiota via the immunoreceptor CD300a. In this study, we showed that commensal microbiota derived exosomes are the one of the other regulatory mechanism of this pathway.

Academic Significance and Societal Importance of the Research Achievements

本研究で、アレルゲンのみではなく、一部の常在菌がケラチノサイトを刺激し、そのケラチノサイトから分泌されるエクソソームが免疫細胞を刺激してサイトカインを分泌させることでTregを制御している可能性が明らかになったことは、常在菌の制御を介したTregの人為的制御によるアレルギー疾患の新たな治療への一歩となりうる。アレルギー疾患は患者数も多く、また、その症状は患者のQOLを著しく低下させることから、Tregを制御することで疾患を克服できれば、社会的な意義は大きい。

Research Products

• [Journal Article] Autonomous regulation of immunoglobulin E-mediated mast cell degranulation and immediate hypersensitivity reaction by an inhibitory receptor CD300a (2019)
  • Author(s): WangY, Nakahashi-Oda C, Okayama Y, Shibuya A
  • Journal Title: J Allergy Clin Immun Volume: 印刷中
  • Peer Reviewed
• [Journal Article] Identification and isolation of splenic tissue resident macrophage subpopulations by flow cytometry (2019)
  • Author(s): Fujiyama S, Nakahashi-Oda C, Abe F, Wang Y, Sato K, Shibuya A
  • Journal Title: Int Immunol Volume: 31(1) Issue: 1 Pages: 51-56
  • DOI: 10.1093/intimm/dxy064
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Elovl6 regulates mechanical damage-induced keratinocyte death and skin inflammation. (2018)
  • Author(s): Nakamura Y, Matsuzaka T, Tahara-Hanaoka S, Shibuya K, Shimano H, Nakahashi-Oda C, Shibuya A.
  • Journal Title: Cell Death Dis. Volume: 9(12) Issue: 12 Pages: 1181-1181
  • DOI: 10.1038/s41419-018-1226-1
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] ホスファチジルセリン受容体CD300aの炎症疾患への関与 (2018)
  • Author(s): 金兼 史佳、小田（中橋）ちぐさ、渋谷 彰
  • Journal Title: 臨床免疫アレルギー科 Volume: 70 Pages: 631-635
• [Journal Article] アポトーシスを起こした上皮細胞による制御性T細胞制御 (2017)
  • Author(s): 小田（中橋）ちぐさ、渋谷 彰
  • Journal Title: 感染・炎症・免疫 Volume: 47 Pages: 205-207
• [Journal Article] CD300a免疫受容体からみえてきた死細胞の炎症反応における役割 (2017)
  • Author(s): 小田（中橋）ちぐさ、渋谷 彰
  • Journal Title: 炎症と免疫 Volume: 25 Pages: 377-382
• [Journal Article] Immunoreceptor CD300a on mast cells and dendritic cells regulates neutrophil recruitment in a murine model of sepsis (2016)
  • Author(s): Udayanga K G S, Nakamura Y, Nakahashi-Oda C, Shibuya A
  • Journal Title: Int Immunol Volume: 28 Issue: 12 Pages: 611-615
  • DOI: 10.1093/intimm/dxw047
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Marginal zone B cells exacerbate endotoxic shock via interleukin-6 secretion induced by Fcα/μR-coupled TLR4 signalling (2016)
  • Author(s): Honda S, Sato K, Totsuka N, Fujiyama S, Fujimoto M, Miyake K, Nakahashi-Oda C, Tahara-Hanaoka S, Shibuya K, Shibuya A
  • Journal Title: Nat Commun Volume: 7 Issue: 1 Pages: 1-10
  • DOI: 10.1038/ncomms11498
  • NAID: 120007135503
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Apoptotic epithelial cells control the abundance of Treg cells at barrier surfaces (2016)
  • Author(s): Nakahashi-Oda C, Udayanga KGS, Nakamura Y, Nakazawa Y, Miki H, Iino S, Tahara-Hanaoka S, Shibuya K, Shibuya A.
  • Journal Title: Nature Immunol, 17(4):441-453, 2016 Volume: 17 Issue: 4 Pages: 441-453
  • DOI: 10.1038/ni.3345
  • Peer Reviewed / Open Access
• [Journal Article] CD300aによる死細胞認識と炎症制御 (2016)
  • Author(s): 中村 貴之;小田,ちぐさ;渋谷 彰
  • Journal Title: 臨床免疫・アレルギー科 Volume: 65 Pages: 241-247
• [Presentation] Self-regulation of mast cell degranulation by an inhibitory receptor CD300a (2019)
  • Author(s): Wang Y, Nakahashi-Oda C, Shibuya A
  • Organizer: 第7回筑波大学・東京理科大学合同リトリート
• [Presentation] Functions of inhibitory receptors of CD300a and CD300lf on mast cells (2019)
  • Author(s): Lyu W, Nakahashi-Oda C, Shibuya A
  • Organizer: 第7回筑波大学・東京理科大学合同リトリート
• [Presentation] Phosphatidylserine exposure self-regulates mast cells degranulation (2018)
  • Author(s): Wang Y, Nakahashi-Oda C, Shibuya A
  • Organizer: 第47回日本免疫学会総会・学術集会
• [Presentation] CD300a による制御性T 細胞の制御メカニズム (2018)
  • Author(s): 中澤 優太、小田 ちぐさ、Kankanam G. S. Udayanga、中村 貴之、三木 春香、 渋谷 彰
  • Organizer: 第83回日本インターフェロン・サイトカイン学会
• [Presentation] Involvement of a new phosphatidylserine receptor, CD300a, in the regulation of Treg cells. (2018)
  • Author(s): Nakahashi-Oda C, Nakazawa Y, Shibuya A
  • Organizer: Australia-Japan Meeting on Cell Death
  • Int'l Joint Research
• [Presentation] 上皮の細胞死によるバリア組織の恒常性の制御 (2017)
  • Author(s): 渋谷 彰、小田 ちぐさ
  • Organizer: 第35回サイトプロテクション研究会
  • Place of Presentation: 京都府京都市
  • Year and Date: 2017-03-10
  • Invited
• [Presentation] Involvement of a new phosphatidylserine receptor, CD300a, in inflammatory diseases (2017)
  • Author(s): Nakahashi-Oda C
  • Organizer: 第46回日本免疫学会総会・学術集会
  • Invited
• [Presentation] 常在細菌叢によるバリア組織の恒常性維持 (2017)
  • Author(s): 渋谷 彰、小田 ちぐさ
  • Organizer: 第66回日本アレルギー学会学術大会
  • Invited
• [Presentation] アポトーシス細胞の貧食シグナルに対する負の制御機構とその生理的意義の解明 (2017)
  • Author(s): 小田 ちぐさ
  • Organizer: 平成29年度新学術領域班会議
• [Presentation] A long-chain fatty-acid elongase, Elovl 6, regulates mechanical stress induced dermatitis. (2017)
  • Author(s): Nakamura Y, Nakahashi-Oda C,
  • Organizer: Keystone Symposia Conference Cell Death and Inflammation
  • Int'l Joint Research
• [Presentation] 腫瘍微小環境におけるCD300aの機能解析 (2017)
  • Author(s): 中澤 優太、小田 ちぐさ
  • Organizer: 第9回血液・疾患免疫療法学会学術集会
• [Presentation] Elovl6 attenuates mechanical stress-induced skin inflammation (2016)
  • Author(s): Nakamura Y, Nakahashi-Oda C, Shibuya A
  • Organizer: 第45回日本免疫学会総会・学術集会
  • Place of Presentation: 沖縄県宜野湾市
  • Year and Date: 2016-12-05
• [Presentation] Apoptotic epithelial cells control the abundance of regulatory T cell at barrier surfaces. (2016)
  • Author(s): Nakazawa Y, Nakahashi-Oda C, Nakamura Y, Udayanga KGS, Shibuya A.
  • Organizer: Immune Profiling in Health and Disease
  • Place of Presentation: アメリカ合衆国、ワシントン州シアトル
  • Year and Date: 2016-10-03
  • Int'l Joint Research
• [Presentation] 常在細菌叢によるバリア組織の恒常性維持 (2016)
  • Author(s): 渋谷 彰、小田 ちぐさ
  • Organizer: 第44回日本臨床免疫学会総会
  • Place of Presentation: 東京都新宿区
  • Year and Date: 2016-09-08
• [Presentation] Apoptotic epithelial cells control the abundance of regulatory T cells at barrier surfaces. (2016)
  • Author(s): Nakahashi-Oda C, Udayanga K. G. S, Nakamura Y, Nakazawa Y, Totsuka N, Miki H, Iino S, Tahara-Hanaoka S, Honda S, Shibuya K, Shibuya A
  • Organizer: International Congress of Immunology 2016
  • Place of Presentation: オーストラリア、ビクトリア州メルボルン
  • Year and Date: 2016-08-05
  • Int'l Joint Research
• [Presentation] 上皮アポトーシス細胞による制御性T細胞数の調節 (2016)
  • Author(s): 小田 ちぐさ
  • Organizer: 第31回自己免疫研究会
  • Place of Presentation: 東京都新宿区
  • Year and Date: 2016-07-23
• [Remarks] 筑波大学免疫学研究室
  • URL: http://immuno-tsukuba.com/index.html
• [Remarks] アポトーシスを起こした上皮細胞と免疫受容体CD300aとの結合が制御性T細胞の数を制御する
  • URL: http://first.lifesciencedb.jp/archives/12163
• [Remarks] 筑波大学免疫学研究室
  • URL: http://immuno-tsukuba.com
• [Patent(Industrial Property Rights)] 活性調節剤 (2017)
  • Inventor(s): 渋谷 彰、小田 ちぐさ
  • Industrial Property Rights Holder: 筑波大学
  • Industrial Property Rights Type: 特許
  • Filing Date: 2017