Role of Autophagy in the Cellular Immunity of Biliary Atresia
Project/Area Number |
18K08535
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 55010:General surgery and pediatric surgery-related
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Research Institution | Chiba Cancer Center (Research Institute) (2020-2022) Chiba University (2018-2019) |
Principal Investigator |
Saito Takeshi 千葉県がんセンター(研究所), がん治療開発グループ がん遺伝創薬研究室, 主任医長 (20406044)
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Co-Investigator(Kenkyū-buntansha) |
幡野 雅彦 千葉大学, 大学院医学研究院, 教授 (20208523)
吉田 英生 千葉大学, 大学院医学研究院, 教授 (60210712)
坂本 明美 千葉大学, バイオメディカル研究センター, 准教授 (90359597)
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Project Period (FY) |
2018-04-01 – 2023-03-31
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Project Status |
Completed (Fiscal Year 2022)
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Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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Keywords | 制御性T細胞 / オートファジー / 胆道閉鎖症 / 先天性胆道拡張症 / 獲得免疫 / 自然免疫 / 免疫応答 / ウイルス感染 / 胆管上皮細胞 / 自己免疫疾患 / 細胞性免疫 / ウェスタンブロティング / 電子顕微鏡 / ウェスタンブロッティング / 小児外科学 |
Outline of Final Research Achievements |
This study investigated the significance and role of regulatory T cell (Treg) and autophagy in the development of the immunological environment of biliary atresia (BA). It revealed that neither frequency or function of Treg in the systemic and local environment did show significant difference compared to the normal controls. On the other hand, the autophagic activities in the systemic CD4 positive cells, in particular Treg, and the local bile duct cells were significantly increased. The effect of the accelerated activity of autophagy in both systemic and local environment on the immunological aspects in BA remains to be clarified.
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Academic Significance and Societal Importance of the Research Achievements |
本研究ではBAの病態について、①全身・局所環境においてTregのfrequencyは低下していなかった、②全身性Tregの機能は低下していなかった、③胆管上皮細胞と全身性T細胞でautophagy機能が亢進していた、④特にCD4/8陽性細胞とTregでautophagy機能が活性化していた、ことが示された。autophagyの機能異常が獲得免疫系を破綻させ、BAの病態を形成している可能性は依然示唆されており、今後の病因研究の方向性を明示している。
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Report
(6 results)
Research Products
(57 results)
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[Journal Article] Clinical outcome of ulcerative colitis with severe onset in children: a multicenter prospective cohort study.2023
Author(s)
Nambu R, Arai K, Kudo T, Murakoshi T, Kunisaki R, Mizuochi T, Kato S, Kumagai H, Inoue M, Ishige T, Saito T, Noguchi A, Yodoshi T, Hagiwara SI, Iwata N, Nishimata S, Kakuta F, Tajiri H, Hiejima E, Toita N, Mochizuki T, Shimizu H, Iwama I, Hirano Y, Shimizu T; JPIBD-R.
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Journal Title
J Gastroenterol.
Volume: Epub ahead of print.
Issue: 5
Pages: 36884071-36884071
DOI
Related Report
Peer Reviewed
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[Journal Article] Frequency and function of circulating regulatory T-cells in biliary atresia.2022
Author(s)
Oita S, Saito T, Sakamoto A, Fujimura L, Ohara Y, Fumita T, Terui K, Nakata M, Komatsu S, Matsuura G, Hatano M, Hishiki T.
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Journal Title
Pediatr Surg Int.
Volume: 30(39)
Issue: 1
Pages: 1-8
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Optimization of surgical timing of congenital diaphragmatic hernia using the quantified flow patterns of patent ductus arteriosus2021
Author(s)
Yoshitaka Shinno, Keita Terui, Mamiko Endo, Takeshi Saito, Mitsuyuki Nakata, Shugo Komatsu, Satoru Oita, Yoshio Katsumata, Yukiko Saeda, Genta Ozeki, Yoshiteru Ohsone, Tomoro Hishiki
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Journal Title
Pediatric Surgery International
Volume: 37
Issue: 2
Pages: 197-203
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Genetic background-dependent abnormalities of the enteric nervous system and intestinal function in Kif26a-deficient mice.2021
Author(s)
Ohara Y, Fujimura L, Sakamoto A, Teratake Y, Hiraoka S, Koseki H, Saito T, Terui K, Mitsunaga T, Nakata M, Yoshida H, Hatano M.
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Journal Title
Sci Rep.
Volume: 4;11(1)
Issue: 1
Pages: 3191-3191
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Phenotypic characteristics of pediatric inflammatory bowel disease in Japan: results from a multicenter registry.2020
Author(s)
Arai K, Kunisaki R, Kakuta F, Hagiwara SI, Murakoshi T, Yanagi T, Shimizu T, Kato S, Ishige T, Aomatsu T, Inoue M, Saito T, Iwama I, Kawashima H, Kumagai H, Tajiri H, Iwata N, Mochizuki T, Noguchi A, Kashiwabara T, Shimizu H, Suzuki Y, Hirano Y, Fujiwara T.
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Journal Title
Intest Res.
Volume: 18
Issue: 4
Pages: 412-420
DOI
Related Report
Peer Reviewed
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[Journal Article] Soluble factors derived from neuroblastoma cell lines suppress dendritic cell differentiation and activation2019
Author(s)
Harada, K., Ihara, F., Takami, M., Kamata, T., Mise, N., Yoshizawa, H., Hishiki, T., Saito, T., Terui, K., Nakata, M., Komatsu, S., Ikeuchi, T., Nakayama, T., Yoshida, H., Motohashi, S.
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Journal Title
Cancer Sci.
Volume: 110
Issue: 3
Pages: 888-902
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] 特殊病態下の輸液管理 先天性横隔膜ヘルニア2019
Author(s)
照井慶太, 遠藤真美子, 中田光政, 小松秀吾, 笈田 諭, 秦 佳孝, 勝俣善夫, 佐永田有季子, 小関元太, 大曽根義輝, 齋藤 武
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Journal Title
小児外科
Volume: 51
Pages: 1130-1133
Related Report
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[Journal Article] Frequency and proliferative response of circulating invariant natural killer T cells in pediatric patients with or without malignant solid tumors.2018
Author(s)
Hishiki T, Mise N, Harada K, Ihara F, Takami M, Saito T, Terui K, Nakata M, Komatsu S, Yoshida H, and Motohashi S
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Journal Title
Pediatr. Surg. Int.
Volume: 34
Issue: 2
Pages: 169-176
DOI
Related Report
Peer Reviewed
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[Journal Article] Invariant natural killer T infiltration in neuroblastoma with favorable outcome.2018
Author(s)
Hishiki T, Mise N, Harada K, Ihara F, Takami M, Saito T, Terui K, Nakata M, Komatsu S, Yoshida H, and Motohashi S
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Journal Title
Pediatr. Surg. Int.
Volume: 34
Issue: 2
Pages: 195-201
DOI
Related Report
Peer Reviewed
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[Presentation] Analysis of the frequency and function of regulatory T-cell using human blood samples in biliary atresia.2019
Author(s)
Oita S, Saito T, Sakamoto A, Terui K, Nakata M, Komatsu S, Harada K, Shinno Y, Fujimura L, Hatano M, Yoshida H.
Organizer
52nd Annual Meeting of the Pacific Association of Pediatric Surgeons
Related Report
Int'l Joint Research
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[Presentation] 胆道閉鎖症の病態形成における制御性T細胞の意義2018
Author(s)
笈田 諭, 齋藤 武, 坂本明美, 照井慶太, 中田光政, 小松秀吾, 原田和 明, 秦 佳孝, 勝海大輔, 古金遼也, 藤村理紗, 幡野雅彦, 吉田英生.
Organizer
第45回日本胆道閉鎖症研究会
Related Report
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