Aberrant differentiation of dendritic cells in malaria infection associated with decreased expression of IRF4/IRF8

• Project/Area Number: 23590492
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Parasitology (including Sanitary zoology)
• Research Institution: Yokohama City University
• Principal Investigator: ICHINO Motohide 横浜市立大学, 医学部, 助教 (60271368)
• Co-Investigator(Renkei-kenkyūsha): TAMURA Tomohiko 横浜市立大学, 医学研究科, 教授 (50285144) ; NISHIYAMA Akira 横浜市立大学, 医学研究科, 准教授 (80589664) ; HOTTA Chie 横浜市立大学, 医学部, 助教 (80363810)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 樹状細胞 / マラリア / 転写因子

Research Abstract

It has been reported that malaria parasite infection suppresses host immune system by interfering with the maturation of dendritic cells (DCs) playing a pivotal role in immune responses. However the molecular mechanisms are not well understood. The present study shows that malaria parasite-infected erythrocytes can interact with host bone-marrow cells and cause aberrant differentiation of DCs by suppressing the transcriptional expression of transcription factors IRF4 and IRF8, by using a mouse model of malaria parasite infection.

Research Products

• [Journal Article] The transcription factor IRF8 counteracts BCR ABL to rescue dendritic cell development in chronic myeloid leukemia (2013)
  • Author(s): Watanabe T, Hotta C, Koizumi S, Miyashita K, Nakabayashi J, Kurotaki K, Sato R G, Yamamoto M, Nakazawa M, Fujita H, Sakai R, Fujisawa S, Nishiyama A, Ikezawa Z, Aihara M, Ishigatsubo Y, Tamura T
  • Journal Title: Cancer Res Volume: 73 (22) Pages: 6642-6653
  • Peer Reviewed
• [Journal Article] Essential role of the IRF8 KLF4 transcription factor cascade in murine monocyte differentiation (2013)
  • Author(s): Kurotaki D, Osato N, Nishiyama A, Yamamoto M, Ban T, Sato H, Nakabayashi J, Umehara M, Miyake N, Matsumoto N, Nakazawa M, Ozato K, Tamura T
  • Journal Title: Blood Volume: 121 (10) Pages: 18391849-18391849
  • Peer Reviewed
• [Journal Article] Introduce My Article"Essential role of the IRF8 KLF4 transcription factor cascade in murine monocyte differentiation (2013)
  • Author(s): 黒滝大翼,田村智彦
  • Journal Title: 臨床血液 Volume: 54 (8) Pages: 786-786
• [Journal Article] IRF8 KLF4転写因子カスケードによる単球分化制御 (2013)
  • Author(s): 黒滝大翼,田村智彦
  • Journal Title: 実験医学 Volume: 31 (18) Pages: 29712975-29712975
• [Journal Article] Shared and distinct functions of the transcription factors IRF4 and IRF8 in myeloid cell development (2011)
  • Author(s): Yamamoto M, Kato T, Hotta C, Nishiyama A, Kurotaki D, Yoshinari M, Takami M, Ichino M, Nakazawa M, Matsuyama T, Kamijo R, Kitagawa S, Ozato K, Tamura T
  • Journal Title: PLoS One Volume: 6
  • Peer Reviewed
• [Journal Article] Shared and distinct functions of the transcription factors IRF4 and IRF8 in myeloid cell development (2011)
  • Author(s): Yamamoto M, et al
  • Journal Title: PLoS ONE Volume: 6 Issue: 10 Pages: e25812-e25812
  • DOI: 10.1371/journal.pone.0025812
  • Peer Reviewed
• [Presentation] IRF8 Inhibits the Activity of C/EBPαto Restrain Monocyte Dendritic Cell Progenitors from Differentiating into Neutrophils (2013)
  • Author(s): Yamamoto M, Kurotaki D, Nishiyama A, Uno K, Ichino M, Nakazawa M, Ozato K, Tamura T
  • Organizer: 第42回日本免疫学会学術集会
  • Place of Presentation: 千葉(口頭発表)
  • Year and Date: 2013-12-13
• [Presentation] IRF8 inhibits the activity of C/EBPαto restrain the neutrophil differentiation program in monocyte dendritic cell progenitors (2013)
  • Author(s): Kurotaki D, Yamamoto M, Nishiyama A, Uno K, Ichino M, Sasaki H, Ban T, Yoshinari M, Nakazawa M, Ozato K, Tamura T
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 神戸(ポスター発表)
  • Year and Date: 2013-12-05
• [Presentation] IRF8 inhibits the activity of C/EBPs to restrain neutrophil development in monocyte DC progenitors (2013)
  • Author(s): Kurotaki D, Yamamoto M, Uno K, Nishiyama A, Nakabayashi J, Morse HC 3rd, Ozato K, Tamura T
  • Organizer: 第75回日本血液学会学術集会
  • Place of Presentation: 札幌(口頭発表)
  • Year and Date: 2013-10-12
• [Presentation] The IRF8 KLF4 transcription factor cascade is essential for the development of monocytes (2013)
  • Author(s): Kurotaki D, Osato N, Nishiyama A, Yamamoto M, Ban T, Sato H, Nakabayashi J, Umehara M, Nakazawa M, Miyake N, Matsumoto N, Ozato K, Tamura T
  • Organizer: 2013 Inaugural Meeting of the International Cytokine and Interferon Society
  • Place of Presentation: San Francisco(ポスター発表)
  • Year and Date: 2013-10-02
• [Presentation] 転写因子IRF8は単球樹状細胞前駆細胞においてC/EBPαの機能を阻害し、好中球分化能の喪失をもたらす (2013)
  • Author(s): 黒滝大翼,山本道雄,宇野和宏,西山晃,中林潤,中津正年,Herbert C. Morse III,Keiko Ozato,田村智彦
  • Organizer: 第24回日本生体防御学会学術総会
  • Place of Presentation: 熊本(口頭発表)
  • Year and Date: 2013-07-12
• [Presentation] The IRF8 KLF4 transcription factor cascade critically regulates the development of inflammatory monocytes (2013)
  • Author(s): Kurotaki D, Osato N, Nishiyama A, Yamamoto M, Ban T, Sato H, Nakabayashi J, Umehara M, Nakazawa M, Miyake N, Matsumoto N, Ozato K, Tamura T
  • Organizer: The Joint International Meeting of the Japanese Society for Interferon and Cytokine Research and Macrophage Molecular and Cellular Biology 2013
  • Place of Presentation: 東京(ポスター発表)
  • Year and Date: 2013-05-20
• [Presentation] ゲノム規模解析による単球分化に重要なIRF8 KLF4転写因子カスケードの発見 (2012)
  • Author(s): 黒滝大翼,大里直樹,西山晃,山本道雄,佐藤英明,中林潤,藩龍馬,梅原莱里奈,三宅紀子,松本直通,中沢正年,Keiko Ozato,田村智彦
  • Organizer: 第35回分子生物学会年会
  • Place of Presentation: 福岡(口頭発表)
  • Year and Date: 2012-12-14
• [Presentation] Genome wide analyses revealed the IRF8 KLF4 transcription factor cascade during monocyte differentiation (2012)
  • Author(s): Kurotaki D, Osato N, Nishiyama A, Yamamoto M, Sato H, Nakabayashi J, Ban T, Ozato K, Tamura T
  • Organizer: 第41回日本免疫学会学術集会
  • Place of Presentation: 神戸(口頭発表)
  • Year and Date: 2012-12-07
• [Presentation] Impaired dendritic cell development in chronic myelogenous leukemia can be rescued by restoring expression of the transcription factor IRF8 (2012)
  • Author(s): Watanabe T, Hotta C, Kurotaki D, Sato RG, Yamamoto M, Nishiyama A, Tamura T
  • Organizer: 第41回日本免疫学会学術集会
  • Place of Presentation: 神戸(口頭発表)
  • Year and Date: 2012-12-07
• [Presentation] The transcription factor IRF8 rescues the dendritic cell development impaired by p210 Bcr/Abl (2011)
  • Author(s): Watanabe T, Hotta C, Sato GR, Yamamoto M, Fujita H, Sakai R, Fujisawa S, Nishiyama A, Aihara M, Ishigatsubo Y, Tamura T
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 横浜(口頭発表)
  • Year and Date: 2011-12-14
• [Presentation] Regulation of the development of monocyte subsets by interferon regulatory factor 8 (2011)
  • Author(s): Kurotaki D, Ichino M, Nishiyama A, Sato G, Yamamoto M, Ozato K, Tamura T
  • Organizer: 第40回日本免疫学会学術総会ワークショップ
  • Place of Presentation: 千葉
  • Year and Date: 2011-11-28
• [Presentation] ミエロイド細胞の分化・機能制御におけるIRF4, IRF8の役割 (2011)
  • Author(s): 山本道雄,加藤隆幸,堀田千絵,西山晃,黒滝大翼,吉成正裕,高見正道,市野素英,中津正年,松山俊文,上保竜太郎,北川誠一,Keiko Ozato,田村智彦
  • Organizer: 第13回神奈川血液・免疫フォーラム
  • Place of Presentation: 相模原(口頭発表)
  • Year and Date: 2011-11-11
• [Presentation] Selective regulation of monocyte subsets by the transcription factor Interferon Regulatory Factor 8 (2011)
  • Author(s): Kurotaki D, Ichino M, Nishiyama A, Sato G, Yamamoto M, Ozato K, Tamura T
  • Organizer: 9th Joint Meeting of the International Society for Interferon and Cytokine Research (ISICR) and the International Cytokine Society (ICS)
  • Place of Presentation: フィレンツェ、イタリア(ポスター)
  • Year and Date: 2011-10-11
• [Presentation] マラリアにおける樹状細胞分化の異常と転写因子IRFファミリー (2011)
  • Author(s): 市野素英,堀田千絵,田村智彦
  • Organizer: 第80回日本寄生虫学会
  • Place of Presentation: 東京(口頭発表)
  • Year and Date: 2011-07-18
• [Presentation] マラリアにおける樹状細胞分化の異常と転写因子IRFファミリー (2011)
  • Author(s): 市野素英，堀田千絵，田村智彦
  • Organizer: 第80回日本寄生虫学会
  • Place of Presentation: 慈恵医大 ( 東京 ）
• [Remarks] 基盤研究(C)の成果発表プログラム(2012年8月4日実施):ひらめきすときめきサイエンス、平成24年度、プログラム名「のぞいてみよう!免疫のしくみ～大食い細胞マクロファージの働き～j研究代表者:市野素英
  • URL: http://www.yokohamacu.ac.jp/hirameki/past/h24/index.html
• [Remarks]
  • URL: http://wwwuser.yokohamacu.ac.jp/~immunol/
• [Remarks] のぞいてみよう！免疫のしくみ～大食い細胞マクロファージの働き～
  • URL: http://www.yokohama-cu.ac.jp/hirameki/h24/index.html