Functions of immune cells for achievement and maintenance of pregnancy

• Project/Area Number: 24592456
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Hyogo Medical University (2016); Hirosaki University (2012-2015)
• Principal Investigator: Fukui Atsushi 兵庫医科大学, 医学部, 講師 (00321969)
• Project Period (FY): 2012-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 生殖医学 / NK細胞 / NCR / サイトカイン / NK22 / NKp46 / 不育症 / 不妊症 / NK22細胞 / IFN-γ / TNF-α / 妊娠高血圧症候群 / 妊娠糖尿病 / 精液 / NCR22 / IFN-g / TNF-a / 精漿 / IL-22 / IL-23

Outline of Final Research Achievements

I evaluated the function of NK cells for achievement and maintenance of pregnancy using pregnant or non-pregnant peripheral blood NK cells, and non-pregnant endometrial or aborted decidual NK cells. The abnormal expression of natural cytotoxicity receptors (NCRs), especially NKp46 on NK cell and the abnormal cytokines production by NK cells are associated with reproductive failures such as recurrent pregnancy loss, infertility and gestational diabetes mellitus. Cytokines production by NK cells may be regulated by NK22 cells. Interestingly, NK cells could be stimulated by partner’s lymphocytes or semen.

Research Products

• [Journal Article] 子宮内膜症に対するLEP製剤投与によるNK細胞の変化 (2016)
  • Author(s): 船水 文乃、福井 淳史、淵之上康平、鴨井 舞衣、福原 理恵、水沼 英樹
  • Journal Title: 日本エンドメトリオーシス学会誌 Volume: 37 Pages: 96-101
  • Peer Reviewed
• [Journal Article] Expression of retinoid-related orphan receptor (ROR)γt on NK22 cells in the peripheral blood and uterine endometrium of women with unexplained recurrent pregnancy loss and unexplained infertility (2016)
  • Author(s): Kohei Fuchinoue, Atsushi Fukui, Hitomi Chiba, Mai Kamoi, Ayano Funamizu, Ayako Taima, Rie Fukuhara and Hideki Mizunuma
  • Journal Title: The Journal of Obstetrical and Gynecology Research Volume: 42 Issue: 11 Pages: 1541-1552
  • DOI: 10.1111/jog.13075
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Expression of Natural Cytotoxicity Receptors on and Intracellular Cytokine Production by NK Cells in Women with Gestational Diabetes Mellitus (2016)
  • Author(s): Chiba, H. Fukui, A. Fuchinoue, K. Funamizu, A. Tanaka, K. Mizunuma, H.
  • Journal Title: Am J Reprod Immunol Volume: 75 Issue: 5 Pages: 529-538
  • DOI: 10.1111/aji.12491
  • Peer Reviewed
• [Journal Article] 1,25-Dihydroxy-vitamin D3 regulates NK-cell cytotoxicity, cytokine secretion, and degranulation in women with recurrent pregnancy losses. (2015)
  • Author(s): Ota K, Dambaeva S, Kim MW, Han AR, Fukui A, Gilman-Sachs A, Beaman K, Kwak-Kim J
  • Journal Title: Eur J Immunol Volume: 45巻 Issue: 11 Pages: 3188-3199
  • DOI: 10.1002/eji.201545541
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] 妊娠の成立と維持におけるNK細胞の機能分担と機能発現 (2015)
  • Author(s): 福井淳史
  • Journal Title: 弘前医学 Volume: 66 Pages: 83-84
  • NAID: 130008049645
  • Peer Reviewed
• [Journal Article] NKp46と生殖 (2015)
  • Author(s): 福井淳史 船水文乃 淵之上康平 千葉仁美 鴨井舞衣 當麻絢子 福原理恵 水沼英樹
  • Journal Title: Reproductive Immunology and Biology Volume: 30 Pages: 1-6
  • NAID: 130005161654
  • Peer Reviewed
• [Journal Article] NK cell abnormality and its treatment in women with recurrent pregnancy loss (2015)
  • Author(s): Fukui, A. Kamoi, M. Funamizu, A. Yokota, M. Fuchinoue, K. Fukuhara, R. Mizunuma, H.
  • Journal Title: Reproductive Medicine and Biology Volume: 14 Pages: 151-157
  • Peer Reviewed
• [Journal Article] NK22 Cells in the Uterine Mid-Secretory Endometrium and Peripheral Blood of Women with Recurrent Pregnancy Loss and Unexplained Infertility (2015)
  • Author(s): Mai Kamoi, Atsushi Fukui, Joanne Kwak-Kim, Kohei Fuchinoue, Ayano Funamizu, Hitomi Chiba, Megumi Yokota, Rie Fukuhara, Hideki Mizunuma
  • Journal Title: American Journal of Reproductive Immunology Volume: 印刷中
  • Peer Reviewed
• [Journal Article] NK cell abnormality and its treatment in women with reproductive failures such as recurrent pregnancy loss, implantation failures, preeclampsia, and pelvic endometriosis (2015)
  • Author(s): Atsushi Fukui, Mai Kamoi, Ayano Funamizu, Kohei Fuchinoue, Hitomi Chiba, Megumi Yokota, Rie Fukuhara, Hideki Mizunuma
  • Journal Title: Reproductive Medicine and Biology Volume: 印刷中
  • Peer Reviewed
• [Journal Article] Expression of Natural Cytotoxicity Receptors on Peritoneal Fluid Natural Killer Cell and Cytokine Production by Peritoneal Fluid Natural Killer Cell in Women with Endometriosis (2014)
  • Author(s): Ayano Funamizu, Atsushi Fukui, Mai Kamoi, Kohei Fuchinoue, Megumi Yokota, Rie Fukuhara, Hideki Mizunuma
  • Journal Title: American Journal of Reproductive Immunology Volume: 71 Issue: 4 Pages: 359-367
  • DOI: 10.1111/aji.12206
  • Peer Reviewed
• [Journal Article] 子宮内膜症における末梢血および腹水中のNK細胞のNCR発現とサイトカイン産生 (2013)
  • Author(s): 船水文乃、福井淳史、横田恵、淵之上康平、鴨井 舞衣、伊東麻美、阿部和弘 福原理恵、水沼英樹
  • Journal Title: 日本エンドメトリオーシス学会誌 Volume: 34 Pages: 113-117
  • Peer Reviewed
• [Journal Article] 体外受精・胚移植における黄体ホルモン腟坐剤を用いた黄体補助時のプロゲステロン濃度と妊娠成績 (2013)
  • Author(s): 福井淳史、福原理恵、鴨井舞衣、船水文乃、伊東麻美、佐々木幸江、中村理果、水沼英樹
  • Journal Title: 日本受精着学会雑誌 Volume: 30 Pages: 223-229
  • Peer Reviewed
• [Journal Article] Role of NKp46 Expression in Cytokine Production by CD56-Positive NK Cells in the Peripheral Blood and the Uterine Endometrium (2013)
  • Author(s): Megumi Yokota, Atushi Fukui, Ayano Funamizu, Rika Nakamura, Mai Kamoi, Kohei Fuchinoue, Yukie Sasaki, Rie Fukuhara, Hideki Mizunuma
  • Journal Title: American Journal of Reproductive Immunology Volume: 69 Issue: 3 Pages: 202-211
  • DOI: 10.1111/aji.12062
  • Peer Reviewed
• [Journal Article] 子宮内膜症における末梢血および腹水中のNK細胞のNCR発現とサイトカイン産生 (2013)
  • Author(s): 船水文乃、福井淳史、横田恵、淵之上康平、鴨井舞衣、伊東麻美、阿部和弘 福原理恵、水沼英樹
  • Journal Title: 日本エンドメトリオーシス学会誌 Volume: 未定
  • Peer Reviewed
• [Presentation] NK細胞異常を有する不妊症・不育症に対する新しい治療法 (2016)
  • Author(s): 福井淳史
  • Organizer: 日本生殖免疫学会
  • Place of Presentation: 神戸国際会議場（兵庫県神戸市）
  • Year and Date: 2016-12-02
  • Invited
• [Presentation] 絨毛組織染色体異常の有無による脱落膜NK22細胞のretinoid-related orphan receptor γt(RORγt)発現についての検討 (2016)
  • Author(s): 淵之上康平、福井淳史、當麻絢子、船水文乃、福原理恵、横山良仁
  • Organizer: 日本生殖免疫学会
  • Place of Presentation: 神戸国際会議場（兵庫県神戸市）
  • Year and Date: 2016-12-02
• [Presentation] 精液を用いた刺激法による子宮内膜NK細胞サイトカイン産生能についての検討 (2016)
  • Author(s): 當麻絢子、福井淳史、淵之上康平、千葉仁美、鴨井舞衣、船水文乃、横山良仁
  • Organizer: 日本生殖免疫学会
  • Place of Presentation: 神戸国際会議場（兵庫県神戸市）
  • Year and Date: 2016-12-02
• [Presentation] The expression of natural cytotoxicity receptors and cytokines production by NK cells for uterine endometrium and peripheral blood in infertile women (2016)
  • Author(s): Atsushi Fukui, Kohei Fuchinoue, Hitomi Chiba, Ayano Funamizu, Ayako Taima, Mai Kamoi, Hideki Mizunuma
  • Organizer: International Society for Immunology of Reproduction
  • Place of Presentation: ドイツ エアフルト
  • Year and Date: 2016-06-22
  • Int'l Joint Research
• [Presentation] Explore the true uterine NK cell cytokines production by the stimulation using semen (2016)
  • Author(s): Ayako Taima, Atsushi Fukui, Kohei Fuchinoue, Hitomi Chiba, Mai Kamoi, Ayano Funamizu, Hideki Mizunuma
  • Organizer: International Society for Immunology of Reproduction
  • Place of Presentation: ドイツ エアフルト
  • Year and Date: 2016-06-22
  • Int'l Joint Research
• [Presentation] Expression of retinoid-related orphan receptor γt (RORγt) on NK22 cells in the peripheral blood and uterine endometrium of women with unexplained recurrent pregnancy loss and unexplained infertility (2016)
  • Author(s): Kohei Fuchinoue, Atsushi Fukui, Hitomi Chiba, Mai Kamoi, Ayano Funamizu, Ayako Taima, Rie Fukuhara, Hideki Mizunuma
  • Organizer: International Society for Immunology of Reproduction
  • Place of Presentation: ドイツ エアフルト
  • Year and Date: 2016-06-22
  • Int'l Joint Research
• [Presentation] Exploration of the couple specific NK1 cell and NK2 cell using male lymphocyte or semen stimulation (2016)
  • Author(s): Atsushi Fukui, Kohei Fuchinoue, Mai Kamoi, Ayano Funamizu, Rie Fukuhara, Hideki Mizunuma
  • Organizer: IFFS regional meeting
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2016-04-26
  • Int'l Joint Research
• [Presentation] Expression of NCRs and RORγt in peripheral blood and endometrial NK cells in women with recurrent pregnancy losses (2016)
  • Author(s): Kohei Fuchinoue, Atsushi Fukui, Mai Kamoi, Ayano Funamizu, Rie Fukuhara, Hideki Mizunuma
  • Organizer: IFFS regional meeting
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2016-04-26
  • Int'l Joint Research
• [Presentation] 不妊症患者子宮内膜および末梢血NK細胞におけるNCR発現とサイトカイン産生と臨床成績 (2016)
  • Author(s): 福井淳史、淵之上康平、千葉仁美、船水文乃、當麻絢子、鴨井舞衣、水沼英樹
  • Organizer: 日本産科婦人科学会
  • Place of Presentation: 東京国際フォーラム（東京都）
  • Year and Date: 2016-04-21
• [Presentation] 不育症患者における末梢血および子宮内膜NK22細胞に対するRORγt発現について (2016)
  • Author(s): 淵之上康平、福井淳史、千葉仁美、鴨井舞衣、船水文乃、當麻絢子、福原理恵、水沼英樹
  • Organizer: 日本産科婦人科学会
  • Place of Presentation: 東京国際フォーラム（東京都）
  • Year and Date: 2016-04-21
• [Presentation] NK cell abnormality and its treatment in women with reproductive failures such as implantation failure and recurrent pregnancy loss (2016)
  • Author(s): Atsushi Fukui, Kohei Fuchinoue, Ayano Funamizu
  • Organizer: 日韓ARTカンファレンス
  • Place of Presentation: ワークピア横浜（神奈川県横浜市）
  • Int'l Joint Research / Invited
• [Presentation] 不育症患者における末梢血および子宮内膜NK22細胞とRORγt発現についての検討 (2015)
  • Author(s): 淵之上康平、福井淳史、當麻絢子、千葉仁美、鴨井舞衣、船水文乃、福原理恵、水沼英樹
  • Organizer: 日本受精着床学会
  • Place of Presentation: TFTホール（東京都江東区）
  • Year and Date: 2015-11-25
• [Presentation] 精液刺激による子宮内膜NK細胞のサイトカイン産生能についての検討 (2015)
  • Author(s): 伊賀千紘、福井淳史、淵之上康平、當麻絢子、千葉仁美、鴨井舞衣、船水文乃、水沼英樹
  • Organizer: 日本受精着床学会
  • Place of Presentation: TFTホール（東京都江東区）
  • Year and Date: 2015-11-25
• [Presentation] 末梢血NK細胞の機能は妊娠時耐糖能と関連するのか (2015)
  • Author(s): 千葉仁美 福井淳史 淵之上康平 船水文乃 田中幹二 水沼英樹
  • Organizer: 日本生殖免疫学会
  • Place of Presentation: くまもと県民交流会館（熊本県熊本市）
  • Year and Date: 2015-11-21
• [Presentation] 不育症患者における末梢血および子宮内膜NK22細胞に対するRORγt発現の関与についての検討 (2015)
  • Author(s): 淵之上康平、福井淳史、千葉仁美、鴨井舞衣、船水文乃、當麻絢子、福原理恵、水沼英樹
  • Organizer: 日本生殖免疫学会
  • Place of Presentation: くまもと県民交流会館（熊本県熊本市）
  • Year and Date: 2015-11-21
• [Presentation] NK cells and reproductive failures such as infertility, implantation failures and recurrent pregnancy loss (2015)
  • Author(s): Atsushi Fukui, Kohei Fuchinoue, Mai Kamoi, Ayano Funamizu, Rie Fukuhara, Hideki Mizunuma
  • Organizer: American society for Reproductive Immunology
  • Place of Presentation: カナダオンタリオ州キングストン
  • Year and Date: 2015-06-02
  • Int'l Joint Research / Invited
• [Presentation] Expression of NCRs and RORγt in peripheral blood and endometrial NK cells in women with recurrent pregnancy losses and unexplained infertility (2015)
  • Author(s): Kohei Fuchinoue, Atsushi Fukui, Mai Kamoi, Ayano Funamizu, Rie Fukuhara, Hideki Mizunuma
  • Organizer: American society for Reproductive Immunology
  • Place of Presentation: カナダオンタリオ州キングストン
  • Year and Date: 2015-06-02
  • Int'l Joint Research
• [Presentation] The relationship of NK22 cells and cytokine production in the uterine mid-secretory endometrium and peripheral blood of women with recurrent pregnancy loss and unexplained infertility (2015)
  • Author(s): M Kamoi, A Fukui, A Funamizu, Y Sasaki, R Nakamura, K Fuchinoue, R Fukuhara, H Mizunuma
  • Organizer: American society for Reproductive Immunology
  • Place of Presentation: カナダオンタリオ州キングストン
  • Year and Date: 2015-06-02
  • Int'l Joint Research
• [Presentation] 不育症患者の子宮内膜と末梢血におけるNK22細胞の役割 (2015)
  • Author(s): 鴨井舞衣、福井淳史、淵之上康平、船水文乃、千葉仁美、横田恵、福原理恵、水沼英樹
  • Organizer: 日本産科婦人科学会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2015-04-09
• [Presentation] 末梢血中および子宮内膜のNK細胞におけるNCRとRORγt発現についての検討 (2015)
  • Author(s): 淵之上康平、福井淳史、鴨井舞衣、船水文乃、福原理恵、水沼英樹
  • Organizer: 日本産科婦人科学会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2015-04-09
• [Presentation] 反復流産患者におけるIL-22産生NK細胞、NK22細胞の解析 (2014)
  • Author(s): 鴨井舞衣 福井淳史 船水文乃 佐々木幸江 中村理果 淵之上康平 福原理恵 水沼英樹
  • Organizer: 日本生殖免疫学会
  • Place of Presentation: 東京都
  • Year and Date: 2014-12-12 – 2014-12-13
• [Presentation] 子宮内膜症の末梢血および腹水中NK細胞NCR発現とサイトカイン産生に対する薬物治療の影響 (2014)
  • Author(s): 船水文乃、福井淳史、淵之上康平、鴨井舞衣、福原理恵、水沼英樹
  • Organizer: 日本生殖免疫学会
  • Place of Presentation: 東京都
  • Year and Date: 2014-12-12 – 2014-12-13
• [Presentation] 不育症患者における末梢血および子宮内膜NK細胞におけるNCRとRORγt発現の関連性 (2014)
  • Author(s): 淵之上康平、福井淳史、鴨井舞衣、船水文乃、福原理恵、水沼英樹
  • Organizer: 日本生殖免疫学会
  • Place of Presentation: 東京都
  • Year and Date: 2014-12-12 – 2014-12-13
• [Presentation] Does immunoglobulin or intralipid work as an immune-modulator for recurrent pregnancy loss women with abnormal NK cells? (2014)
  • Author(s): Atsushi Fukui, Mai Kamoi, Ayano Funamizu, Kohei Fuchinoue, Megumi Yokota, Rie Fukuhara, Hideki Mizunuma
  • Organizer: American Society for Reproductive Immunology
  • Place of Presentation: Long Beach, NY
  • Year and Date: 2014-06-02 – 2014-06-05
• [Presentation] Natural cytotoxicity receptors expression and cytokines production of natural killer cells in peripheral blood and peritoneal fluid in patients with endometriosis (2014)
  • Author(s): Ayano Funamizu, Atsushi Fukui, Mai Kamoi, Kohei Fuchinoue, Megumi Yokota, Rie Fukuhara, Hideki Mizunuma
  • Organizer: American Society for Reproductive Immunology
  • Place of Presentation: Long Beach, NY
  • Year and Date: 2014-06-02 – 2014-06-05
• [Presentation] The function of uterine and peripheral blood NK22 cells in women with reproductive failures (2014)
  • Author(s): Mai Kamoi, Atsushi Fukui, Ayano Funamizu, Kohei Fuchinoue, Megumi Yokota, Rie Fukuhara, Hideki Mizunuma
  • Organizer: American Society for Reproductive Immunology
  • Place of Presentation: Long Beach, NY
  • Year and Date: 2014-06-02 – 2014-06-05
• [Presentation] 末梢血Natural Killer細胞のNatural Cytotoxicity Receptor発現とサイトカイン産生は子宮内膜症で変わるのか？ (2014)
  • Author(s): 船水文乃、福井淳史、鴨井舞衣、淵之上康平、横田恵、福原理恵、水沼英樹
  • Organizer: 日本産科婦人科学会
  • Place of Presentation: 東京都
  • Year and Date: 2014-04-18 – 2014-04-20
• [Presentation] NK細胞異常を有する不育症患者にγグロブリンは有用か？ (2014)
  • Author(s): 鴨井舞衣 福井淳史 船水文乃 淵之上康平 福原理恵 水沼英樹
  • Organizer: 日本産科婦人科学会
  • Place of Presentation: 東京都
  • Year and Date: 2014-04-18 – 2014-04-20
• [Presentation] Should biochemical pregnancy be categorized as miscarriage? (2013)
  • Author(s): Atsushi Fukui, Mai Kamoi, Ayano Funamizu, Asami Ito, Megumi Yokota, Rie Fukuhara, Hideki Mizunuma
  • Organizer: International Society for Immunology of Reproduction
  • Place of Presentation: Boston, MA, USA
• [Presentation] The expression of Natural Cytotoxicity Receptors and NK cell cytokines production in women with endometriosis (2013)
  • Author(s): Ayano Funamizu, Atsushi Fukui, Mai Kamoi, Megumi Yokota, Rie Fukuhara, Hideki Mizunuma
  • Organizer: International Society for Immunology of Reproduction
  • Place of Presentation: Boston, MA, USA
• [Presentation] The function of NCR22 cells in endometrium and peripheral blood obtained from women with recurrent pregnancy loss (2013)
  • Author(s): M Kamoi, A Fukui, A Funamizu, A Ito, M Yokota, R Fukuhara, H Mizunuma
  • Organizer: International Society for Immunology of Reproduction
  • Place of Presentation: Boston, MA, USA
• [Presentation] 生殖における末梢血IL-22産生NK細胞の機能 (2013)
  • Author(s): 船水文乃 福井淳史 横田恵 淵之上康平 鴨井舞衣 福原理恵 水沼英樹
  • Organizer: 日本産科婦人科学会
  • Place of Presentation: 札幌市
• [Presentation] 黄体期中期の末梢血および子宮内膜NK細胞におけるNKp46発現とサイトカイン産生の関係について (2013)
  • Author(s): 横田恵、福井淳史、鴨井舞衣、船水文乃、福原理恵、水沼英樹
  • Organizer: 日本産科婦人科学会
  • Place of Presentation: 札幌市
• [Presentation] Recent progress of study on endometrial NK cells function in human reproduct (2013)
  • Author(s): Atsushi Fukui
  • Organizer: International Conference on Reproductive Immunology
  • Place of Presentation: 上海、中国
  • Invited
• [Presentation] Natural Cytotoxicity Receptors Expression and cytokines production of Natural Killer cells in peripheral blood and peritoneal fluid in women with endometriosis (2013)
  • Author(s): Ayano Funamizu, Atsushi Fukui, Mai Kamoi, Kohei Fuchinoue, Megumi Yokota, Rie Fukuhara, Hideki Mizunuma
  • Organizer: International Conference on Reproductive Immunology
  • Place of Presentation: 上海、中国
  • Invited
• [Presentation] 不育症診療におけるNK細胞の関与とその適正化 (2013)
  • Author(s): 福井淳史
  • Organizer: 日本生殖医学会
  • Place of Presentation: 兵庫県神戸市
  • Invited
• [Presentation] Are there any abnormal NK cells in women with recurrent pregnancy loss? (2013)
  • Author(s): Atsushi Fukui
  • Organizer: 日本生殖免疫学会
  • Place of Presentation: 兵庫県西宮市
  • Invited
• [Presentation] NK細胞の異常は、不妊症・不育症をもたらすのか？ (2012)
  • Author(s): 福井淳史、船水文乃、横田恵、福原理恵、水沼英樹
  • Organizer: 日本生殖免疫学会
  • Place of Presentation: 高槻市
  • Invited
• [Presentation] 生殖におけるNCR22細胞の機能 (2012)
  • Author(s): 船水文乃、福井淳史、横田恵、淵之上康平、鴨井舞衣、福原理恵、水沼英樹
  • Organizer: 日本生殖免疫学会
  • Place of Presentation: 高槻市