Frequency and function of regulatory T cell subpopulation of biliary atresia

• Project/Area Number: 15K10917
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatric surgery
• Research Institution: Chiba University
• Principal Investigator: Saito Takeshi 千葉大学, 大学院医学研究院, 准教授 (20406044)
• 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)
• Co-Investigator(Renkei-kenkyūsha): SHIBATA Ryouhei 千葉大学, 医学部附属病院, 医員 (90748766) ; OITA Satoru 千葉大学, 医学部附属病院, 医員 (90813543)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 制御性T細胞 / 胆道閉鎖症 / 自然免疫 / 小児外科学 / 機能解析 / subpopulation / 免疫学

Outline of Final Research Achievements

We investigated the frequency and function of Treg subpopulation in the systemic and local cellular immunity, using not only generally accepted Treg marker (CD4, CD25, FoxP3) but also additional markers (CD45RA, CD127, and Helios). Even though no difference was found in the frequency and lymphocyte suppression capacity of CD4+CD25+FoxP3 cells found both in the systemic and local immunological environment between BA group and control group, those of CD4+CD25+CD45RA-CD127- cells were significantly lower in BA group than control group. In terms of hepatic immune environment, the frequency of CD4+CD25+FoxP3 cells did not yield significant difference between the groups, while that of CD4+CD25+CD45RA-CD127- cells was significantly lower than the control group. Thus, Treg subpopulation may be showing the different immunological behavior from conventional CD4+CD25+ Treg cells, possibly leading to the etiology and pathology of BA.

Research Products

• [Journal Article] 先天性胆道拡張症の最前線．先天性胆道拡張症の画像診断. (2017)
  • Author(s): 齋藤 武，照井慶太, 中田光政, 小松秀吾, 小原由紀子，柴田涼平，原田和明，文田貴志，西村雄宏，吉田英生.
  • Journal Title: 胆と膵 Volume: 38 Pages: 343-349
• [Journal Article] Serial Radiographic Imaging For Real-Time Evaluation of Blood Flow During Low Anterior Resection: Initial Study in a Porcine Model. (2017)
  • Author(s): Kawahira H, Saito T, Ohnishi T, Haneishi H.
  • Journal Title: Int Surg Volume: -
  • Peer Reviewed
• [Journal Article] Classification of pancreaticobiliary maljunction and clinical features in children. (2017)
  • Author(s): Urushihara N, Hamada Y, Kamisawa T, Fujii H, Koshinaga T, Morotomi Y, Saito T, Itoi T, Kaneko K, Fukuzawa H, Ando H.
  • Journal Title: J Hepatobiliary Pancreat Sci. Volume: 24 Issue: 8 Pages: 449-455
  • DOI: 10.1002/jhbp.485
  • Peer Reviewed
• [Journal Article] Usefulness of 99mTc-DTPA galactosyl human serum albumin liver scintigraphy for evaluating hepatic functional reserve after Kasai procedure. (2017)
  • Author(s): Mitsunaga T, Higashimoto Y, Saito T, Iwai J.
  • Journal Title: J Pediatr Surg. Volume: 52 Issue: 12 Pages: 1925-1929
  • DOI: 10.1016/j.jpedsurg.2017.08.058
  • Peer Reviewed
• [Journal Article] Prediction of respiratory collapse among pediatric patients with mediastinal tumors during induction of general anesthesia. (2017)
  • Author(s): Kawaguchi Y, Saito T, Mitsunaga T, Terui K, Nakata M, Matsuura G, Kouchi K, Yoshida H.
  • Journal Title: J Pediatr Surg. Volume: - Issue: 7 Pages: 30612-7
  • DOI: 10.1016/j.jpedsurg.2017.09.013
  • Peer Reviewed
• [Journal Article] 【新生児・乳児消化管アレルギー】 新生児外科疾患術後発症症例． (2017)
  • Author(s): 光永哲也, 齋藤 武, 照井慶太, 中田光政, 小松秀吾, 吉田英生．
  • Journal Title: 小児外科 Volume: 49 Pages: 727-730
• [Journal Article] 小児24時間食道インピーダンスpHモニタリングプロトコール． (2017)
  • Author(s): 川原央好, 深堀 優, 田中 彩, 尾山貴徳, 羽鳥麗子, 齋藤 武, 藤野順子, 野田卓男, 下野隆一, 八木 実, 日本小児消化管機能研究会日本小児食道インピーダンスpHモニタリングワーキンググループ．
  • Journal Title: 日小外会誌 Volume: 53 Pages: 1215-1219
  • NAID: 130006177810
• [Journal Article] Systemic and local cytokine profile in biliary atresia. (2016)
  • Author(s): Saito T, Sakamoto A, Hatano M, Iwai J, Higashimoto Y, Yoshida H.
  • Journal Title: Eur J Pediatr Surg Volume: ー Issue: 03 Pages: 280-287
  • DOI: 10.1055/s-0036-1592136
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Significance of imaging modalities for preoperative evaluation of the pancreaticobiliary system in surgery for pediatric choledochal cyst. (2016)
  • Author(s): Saito T, Terui K, Mitsunaga T, Nakata M, Yoshida H.
  • Journal Title: J Hepatobiliary Pancreat Sci. Volume: 23 Issue: 6 Pages: 347-52
  • DOI: 10.1002/jhbp.347
  • Peer Reviewed
• [Journal Article] Ellis-van Creveld syndrome associated with chronic intestinal pseudo-obstruction. (2016)
  • Author(s): Iwakura H, Fujii K, Furutani Y, Takatani T, Ebata R, Nakanishi T, Mitsunaga T, Saito T, Kishimoto T, Yoshida H, Shimojo N.
  • Journal Title: Pediatr Int. Volume: 58 Issue: 1 Pages: 64-6
  • DOI: 10.1111/ped.12846
  • Peer Reviewed
• [Journal Article] Antibody-dependent cellular cytotoxicity toward neuroblastoma enhanced by activated invariant natural killer T cells. (2016)
  • Author(s): Mise N, Takami M, Suzuki A, Kamata T, Harada K, Hishiki T, Saito T, Terui K, Mitsunaga T, Nakata M, Ikeuchi T, Nakayama T, Yoshida H, Motohashi S
  • Journal Title: Cancer Science Volume: 107 Issue: 3 Pages: 233-241
  • DOI: 10.1111/cas.12882
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] 周産期医学必修知識第8版 胆道閉鎖症 (2016)
  • Author(s): 齋藤 武、吉田英生．
  • Journal Title: 周産期医学 Volume: 46増刊 Pages: 787-90
• [Journal Article] Diagnostic criteria for congenital biliary dilatation 2015. (2016)
  • Author(s): Hamada Y, Ando H, Kamisawa T, Itoi T, Urushihara N, Koshinaga T, Saito T, Fujii H, Morotomi Y.
  • Journal Title: J Hepatobiliary Pancreat Sci. Volume: 23 Issue: 6 Pages: 342-6
  • DOI: 10.1002/jhbp.346
  • NAID: 130005119506
  • Peer Reviewed
• [Journal Article] Evidence for viral infection as a causative factor of human biliary atresia. (2015)
  • Author(s): Saito T, Terui K, Mitsunaga T, Nakata M, Ono S, Mise N, Yoshida H.
  • Journal Title: J Pediatr Surg. Volume: 50 Issue: 8 Pages: 1398-1404
  • DOI: 10.1016/j.jpedsurg.2015.04.006
  • Peer Reviewed
• [Journal Article] Oncolytic viral therapy for neuroblastoma cells with Sindbis virus AR339 strain. (2015)
  • Author(s): Takenouchi A, Saito K, Saito E, Saito T, Hishiki T, Matsunaga T, Isegawa N, Yoshida H, Ohnuma N, Shirasawa H.
  • Journal Title: Pediatr Surg Int. Volume: 31 Issue: 12 Pages: 1151-1159
  • DOI: 10.1007/s00383-015-3784-y
  • Peer Reviewed / Open Access
• [Journal Article] 乳児期先天性胆道拡張症手術後26年で肝切除施行した術後肝内結石症の1例． (2015)
  • Author(s): 榛澤侑介，高屋敷吏，内玲往那，齋藤 武，吉田英生，宮崎 勝．
  • Journal Title: 日臨外会誌． Volume: 76 Pages: 1463-1468
  • NAID: 130005116753
  • Peer Reviewed
• [Presentation] Significance and Indication of Revision in Biliary Atresia (2017)
  • Author(s): Saito T, Terui K, Nakata M, Komatsu S, Ohara Y, Shibata R, Harada K, Fumita T, Nishimura K, Yoshida H.
  • Organizer: 50th Annual Meeting of the Pacific Association of Pediatric Surgeons
  • Place of Presentation: Seattle Marriott Waterfront 2100 Alaskan Way Seattle, Washington USA
  • Year and Date: 2017-05-29
  • Int'l Joint Research
• [Presentation] Significance and Indication of Revision in Biliary Atresia (2017)
  • Author(s): Saito T, Terui K, Nakata M, Komatsu S, Ohara Y, Shibata R, Harada K, Fumita T, Nishimura K, Yoshida H.
  • Organizer: The 7th International Sendai Symposium on Biliary Atresia (7th ISSBA)
  • Place of Presentation: Sendai International Center, Sendai, Miyagi
  • Year and Date: 2017-05-12
  • Int'l Joint Research
• [Presentation] Significance and Indication of Revision in Biliary Atresia. 50th Annual Meeting of the Pacific Association of Pediatric Surgeons. (2017)
  • Author(s): Saito T, Terui K, Nakata M, Komatsu S, Yoshida H.
  • Organizer: 50th Annual Meeting of the Pacific Association of Pediatric Surgeons.
  • Int'l Joint Research
• [Presentation] Alonso-Lej/戸谷分類Ⅱ型のvariationと課題． (2017)
  • Author(s): 齋藤 武，照井慶太，中田光政，小松秀吾，柴田涼平，原田和明，勝俣善夫，西村雄宏，勝海大輔，吉田英生．
  • Organizer: 第40回日本膵・胆管合流異常研究会．
• [Presentation] Significance and Indication of Revision in Biliary Atresia. (2017)
  • Author(s): Saito T, Terui K, Nakata M, Komatsu S, Ohara Y, Shibata R, Harada K, Fumita T, Nishimura K, Yoshida H.
  • Organizer: 第54回日本小児外科学会学術集会．
• [Presentation] 当科における胆道閉鎖症(BA)の再手術の意義と適応について． (2016)
  • Author(s): 212.齋藤 武，照井慶太，光永哲也，中田光政，三瀬直子，小原由紀子，川口雄之亮，吉田英生．
  • Organizer: 第53回日本小児外科学会学術集会．
  • Place of Presentation: 福岡県福岡市 ヒルトン福岡シーホーク
• [Presentation] BA再手術適応の統計学的検討． (2016)
  • Author(s): 217.齋藤 武，照井慶太，中田光政，小松秀吾，小原由紀子，柴田涼平，原田和明，西村雄亮，文田貴志，吉田英生．
  • Organizer: 第43回日本胆道閉鎖症研究会．
  • Place of Presentation: 新潟県新潟市 朱鷺メッセ 新潟コンベンションセンター
• [Presentation] 当科における胆道閉鎖症(BA)の肝移植以外再手術の意義について． (2015)
  • Author(s): 齋藤 武，照井慶太，光永哲也，中田光政，三瀬直子，小原由紀子，川口雄之亮，吉田英生．
  • Organizer: 第42回日本胆道閉鎖症研究会
  • Place of Presentation: 東京大学山上会館(東京都文京区)
  • Year and Date: 2015-11-07
• [Presentation] 胆道閉鎖症(Biliary Atresia; BA)のウイルス感染説のエビデンス． (2015)
  • Author(s): 齋藤 武，照井慶太，光永哲也，中田光政，吉田英生．
  • Organizer: 第42回日本小児栄養消化器肝臓学会
  • Place of Presentation: 広島国際会議場(広島県広島市)
  • Year and Date: 2015-10-16
• [Presentation] 当科における小児先天性胆道拡張症術後肝内結石症例の臨床的検討． (2015)
  • Author(s): 齋藤 武，照井慶太，光永哲也，中田光政，三瀬直子，小原由紀子，川口雄之亮，露口利夫，高屋敷吏，宮崎 勝，吉田英生．
  • Organizer: 第38回日本膵・胆管合流異常研究会
  • Place of Presentation: 新潟県医師会館(新潟県新潟市)
  • Year and Date: 2015-09-12
• [Presentation] Management Strategy for Intrahepatic Calculi after Radical Surgery for Pediatric Choledochal Cyst. (2015)
  • Author(s): Saito T, Terui K, Mitsunaga T, Nakata M, Yoshida H.
  • Organizer: 62nd Annual International Conference of the British Association of Pediatric Surgeons.
  • Place of Presentation: City Hall, Cardiff, United Kingdom.
  • Year and Date: 2015-07-22
  • Int'l Joint Research
• [Presentation] 当科の胆道閉鎖症(Biliary Atresia; BA)疑い症例に対する診断アプローチとその成績． (2015)
  • Author(s): 齋藤 武、照井慶太、光永哲也、中田光政、吉田英生．
  • Organizer: 第52回日本小児外科学会学術集会
  • Place of Presentation: 神戸国際会議場(兵庫県神戸市)
  • Year and Date: 2015-05-28
• [Presentation] 胆道閉鎖症におけるTh17/TregバランスとTregの意義． (2015)
  • Author(s): 齋藤 武、小原由紀子、坂本明美、照井慶太、光永哲也、中田光政、大野幸恵、三瀬直子、幡野雅彦、吉田英生．
  • Organizer: 第52回日本小児外科学会学術集会
  • Place of Presentation: 神戸国際会議場(兵庫県神戸市)
  • Year and Date: 2015-05-28
• [Book] 小児消化器内視鏡ガイドライン2017． (2017)
  • Author(s): 日本小児栄養消化器肝臓学会．
  • Total Pages: 116
  • Publisher: 診断と治療社．
• [Book] ナースの外科学改訂7版． (2017)
  • Author(s): 齋藤 武，吉田英生, 他.
  • Total Pages: 566
  • Publisher: 中外医学社.