Clarification of molecular mechanisms for regulating dendritic cell subset functions

2013 Fiscal Year Final Research Report

• Project/Area Number: 23390124
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Immunology
• Research Institution: Osaka University
• Principal Investigator: KAISHO Tsuneyasu 大阪大学, 免疫学フロンティア研究センター, 寄附研究部門教授 (60224325)
• Project Period (FY): 2011-04-01 – 2014-03-31
• Keywords: 樹状細胞 / インターフェロン / クロスプライミング / シグナル伝達

Research Abstract

Dendritic cells (DCs) consist of various subsets and functions in a subset-specific manner. Plasmacytoid DC (PDC) produce type I interferons (IFNs) in response to the signaling through nucleic acid sensors, TLR7/9, thereby being involved in antiviral defense and pathogenesis of certain autoimmune diseases. An Ets family transcription factor, Spi-B, highly expressed in PDC, is critical for this PDC activity. Furthremore, CD8alpha+ DC is featured by its high crosspresenting ability. The mutant mice, in which CD8alpha+ DC can be traced by fluorescence protein expression and ablated conditionally, were generated. By using the mice, CD8alpha+ DC was found to be critical for in vivio crosspresentation. Thus, molecular and cellular mechansims on the DC subset-specific functions were clarified.

Research Products

• [Journal Article] Olfactory Plays a Key Role in Spatiotemporal Pathogenesis of Cerebral Malaria (2014)
  • Author(s): H. Zhao, T. Aoshi, S. Kawai, Y. Mori, A. Konishi, M. Ozkan, Y. Fujita, Y. Haseda, M. Shimizu, M. Kohyama, K. Kobiyama, K. Eto, J. Nabekura, T. Horii, T. Ishino, M. Yuda, H. Hemmi, T. Kaisho, S. Akira, M. Kinoshita, K. Tohyama, Y. Yoshioka, K. J. Ishii, C. Coban
  • Journal Title: Cell Host Microbe Volume: 15 Pages: 551-563
  • DOI: 10.1016/j.chom.2014.04.008
  • Peer Reviewed
• [Journal Article] Enhanced Apoptosis by Disruption of the STAT3-IκB-ζ Signaling Pathway in Epithelial Cells Induces Sjögren's Syndrome-like Autoimmune Disease (2013)
  • Author(s): A. Okuma, K. Hoshino, T. Ohba, S. Fukushi, S. Aiba, S. Akira, M. Ono, T. Kaisho, T. Muta
  • Journal Title: Immunity Volume: 38 Pages: 450-460
  • DOI: 10.1016/j.immuni.2012.11.016
  • Peer Reviewed
• [Journal Article] Double-stranded RNA of small intestinal commensal but not pathogenic bacteria triggers TLR3-mediated IFN-β production by dendritic cells (2013)
  • Author(s): T. Kawashima, A. Kosaka, H. Yan, G. Zijin, R. Uchiyama, R. Fukui, D. Kaneko; Y. Kumagai; D.-J. You, J. Carreras, S. Uematsu, M. H. Jang, O. Takeuchi, T. Kaisho, S. Akira, K. Miyake, H. Tsutsui, T. Saito, I. Nishimura, N. M. Tsuji
  • Journal Title: Immunity Volume: 38 Pages: 1187-1197
  • DOI: 10.1016/j.immuni.2013.02.024
  • Peer Reviewed
• [Journal Article] Invariant NKT cells induce plasmacytoid DC cross-talk with conventional DCs for efficient memory CD8+ T cell induction (2013)
  • Author(s): K. Shimizu, M. Asakura, J. Shinga, Y. Sato, S. Kitahara, K. Hoshino, T. Kaisho, S. P. Schonberger, T. Ezaki, S. I. Fujii
  • Journal Title: J. Immunol Volume: 190 Pages: 5609-5619
  • DOI: 10.4049/jimmunol.1300033
  • Peer Reviewed
• [Journal Article] Critical roles of a dendritic cell subset expressing a chemokine receptor, XCR1 (2013)
  • Author(s): C. Yamazaki, M. Sugiyama, T. Ohta, H. Hemmi, E. Hamada, I. Sasaki, Y. Fukuda, T. Yano, M. Nobuoka, T. Hirashima, A. Iizuka, K. Sato, T. Tanaka, K. Hoshino, T. Kaisho
  • Journal Title: J. Immunol Volume: 190 Pages: 6071-6082
  • DOI: 10.4049/jimmunol.1202798
  • Peer Reviewed
• [Journal Article] 自然免疫とアレルギー (2013)
  • Author(s): 改正恒康
  • Journal Title: アレルギー Volume: 62(7) Pages: 789-796
• [Journal Article] Pathogen sensors and chemokine receptors in dendritic cell subsets (2012)
  • Author(s): T. Kaisho
  • Journal Title: Vaccine Volume: 30 Pages: 7652-7657
  • DOI: 10.1016/j.vaccine.2012.10.043
  • Peer Reviewed
• [Journal Article] Treml4, an Ig Superfamily Member, Mediates Presentation of Several Antigens to T Cells In Vivo, Including Protective Immunity to HER2 Protein (2012)
  • Author(s): H. Hemmi, N. Zaidi, B. Wang, I. Matos, C. Fiorese, A. Lubkin, L. Zbytnuik, K. Suda, K. Zhang, M. Noda, T. Kaisho, R. M. Steinman, J. Idoyaga
  • Journal Title: J. Immunol Volume: 188 Pages: 1147-1155
  • DOI: 10.4049/jimmunol.1102541
  • Peer Reviewed
• [Journal Article] Differential MyD88/IRAK4 requirements for cross-priming and tumor rejection induced by heat shock protein 70-model antigen fusion protein (2012)
  • Author(s): S. Mizukami, C. Kajiwara, M. Tanaka, T. Kaisho, H. Udono
  • Journal Title: Cancer Sci Volume: 103(5) Pages: 851-9
  • DOI: 10.1111/j.1349-7006.2012.02233.x
  • Peer Reviewed
• [Journal Article] The Ets transcription factor Spi-B is essential for the differentiation of intestinal microfold cells (2012)
  • Author(s): T. Kanaya, K. Hase, D. Takahashi, S. Fukuda, K. Hoshino, I. Sasaki, H. Hemmi, K.A. Knoop, N. Kumar, M. Sato, T. Katsuno, O. Yokosuka, K. Toyooka, K. Nakai, A. Sakamoto, Y. Kitahara, T. Jinnohara, S.J. McSorley, T. Kaisho, I.R. Williams, H. Ohno
  • Journal Title: Nat Immunol Volume: 13(8) Pages: 729-36
  • DOI: 10.1038/ni.2352
  • Peer Reviewed
• [Journal Article] Spi-B is critical for plasmacytoid dendritic cell function and development (2012)
  • Author(s): I. Sasaki, K. Hoshino, T. Sugiyama, C. Yamazaki, T. Yano, A. Iizuka, H. Hemmi, T. Tanaka, M. Saito, M. Sugiyama, Y. Fukuda, T. Ohta, K. Sato, A. Ainai, T. Suzuki, H. Hasegawa, N. Toyama-Sorimachi, H. Kohara, T. Nagasawa, T. Kaisho
  • Journal Title: Blood Volume: 120 Pages: 4733-4743
  • DOI: 10.1182/blood-2012-06-436527
  • Peer Reviewed
• [Journal Article] Lactococcus lactis subsp. cremoris FC triggers IFN-γ production from NK and T cells via IL-12 and IL-18 (2012)
  • Author(s): A. Kosaka, H. Yan, S. Ohashi, Y. Gotoh, A. Sato, H. Tsutsui, T. Kaisho, T. Toda, Tsuji NM
  • Journal Title: Int Immunopharmacol Volume: 14(4) Pages: 729-33
  • DOI: 10.1016/j.intimp.2012.10.007
  • Peer Reviewed
• [Journal Article] CD8 陽性樹状細胞サブセットの動的制御機構の解析 (2012)
  • Author(s): 邊見弘明, 山崎千尋, 星野克明, 改正恒康
  • Journal Title: Cytometry Research Volume: 22(1) Pages: 31-35
• [Journal Article] 樹状細胞サブセットの機能と生理的意義 (2012)
  • Author(s): 佐々木泉, 改正恒康
  • Journal Title: 炎症と免疫 Volume: 20(1) Pages: 21-26
• [Journal Article] 樹状細胞に関する私の初仕事 (2012)
  • Author(s): 改正恒康
  • Journal Title: アレルギ - の臨床 Volume: 32(12) Pages: 13
• [Journal Article] PDLIM2 inhibits T helper cell development and granulomatous inflammation through degradation of STAT3 (2011)
  • Author(s): T. Tanaka, Y. Yamamoto, R. Muromoto, O. Ikeda, Y. Sekine, M. J. Grusby, T. Kaisho, T. Matsuda
  • Journal Title: Sci. Signal Volume: 4(202) Pages: ra85
  • DOI: 10.1126/scisignal.2001637
  • Peer Reviewed
• [Journal Article] Plasmacytoid dendritic cells are crucial for the initiation of inflammation and T cell immunity in vivo (2011)
  • Author(s): H. Takagi, T. Fukaya, K. Eizumi, Y. Sato, K. Sato, A. Shibazaki, H. Otsuka, A. Hijikata, T. Watanabe, O. Ohara, T. Kaisho, B. Malissen, K. Sato
  • Journal Title: Immunity Volume: 35 Pages: 958-971
  • DOI: 10.1016/j.immuni.2011.10.014
  • Peer Reviewed
• [Journal Article] 免疫アジュバントの特性と Th 細胞分化誘導 (2011)
  • Author(s): 大田友和, 改正恒康
  • Journal Title: 臨床免疫・アレルギー科 Volume: 56(5) Pages: 558-563
• [Journal Article] 樹状細胞サブセット機能を制御する分子機構 (2011)
  • Author(s): 改正恒康
  • Journal Title: アレルギー Volume: 60(5) Pages: 559-565
• [Presentation] The transcription factor IRF8 is required for basophil development (2013)
  • Author(s): H. Sasaki, D. Kurotaki, N. Osato, I. Sasaki, C. Kaneda, A. Nishiyama, T.Kaisho , H. C. III. Morse, K. Ozato, T. Tamura
  • Organizer: 第42回日本免疫学会総会
  • Place of Presentation: 幕張メッセ
  • Year and Date: 20131211-13
• [Presentation] Double-stranded RNA of intestinal commensal but not pathogenic bacteria triggers production of protective IFN- β (2013)
  • Author(s): T. Kawashima, H Yan, Z. Guo, J. Carreras, R. Uchiyama, R. Fukui, T. Kaisho , S. Akira, K. Miyake, H. Tsutsui, T. Saito, N.M.Tsuji
  • Organizer: 第42回日本免疫学会総会
  • Place of Presentation: 幕張メッセ
  • Year and Date: 20131211-13
• [Presentation] A novel mechanism to generate the intestinal intraepithelial T lymphocytes by XCR-expressing dendric cells (2013)
  • Author(s): T. Ohta, H. Hemmi, C. Yamazaki, M. Sugiyama, I. Sasaki, K. Hoshino, T. Kaisho
  • Organizer: 第42回日本免疫学会総会
  • Place of Presentation: 幕張メッセ
  • Year and Date: 20131211-13
• [Presentation] Function of XCR1-expressing dendric cells in oral tolerance (2013)
  • Author(s): H. Hemmi, M. Sugiyama, T. Ohta, I. Sasaki, C. Yamazaki, T. Tanaka, K. Hoshino, T. Kaisho
  • Organizer: 第42回日本免疫学会総会
  • Place of Presentation: 幕張メッセ
  • Year and Date: 20131211-13
• [Presentation] Long-term memory T cell response induced by adjuvant role of iNKT cells (2013)
  • Author(s): K. Shimizu, Y. Sato, J. Shinga, M. Asakura, T. Kaisho
  • Organizer: 第42回日本免疫学会総会
  • Place of Presentation: 幕張メッセ
  • Year and Date: 20131211-13
• [Presentation] Lactococcus lactis subsp. cremoris FC triggers IFN-ɤproduction from NK and T cells via IL-12 and IL-18 (2013)
  • Author(s): Kosaka, H. Yan, H. Tsutsui, T. Kaisho , N. Tsuji
  • Organizer: 第42回日本免疫学会総会
  • Place of Presentation: 幕張メッセ
  • Year and Date: 20131211-13
• [Presentation] The role of M cells in intestinal helminthic infection (2013)
  • Author(s): C. Shimokawa, T. Kanaya, T. Kaisho
  • Organizer: 第42回日本免疫学会総会
  • Place of Presentation: 幕張メッセ
  • Year and Date: 20131211-13
• [Presentation] In vivo roles of XCR1-expressing dendric cells (2013)
  • Author(s): T. Kaisho
  • Organizer: 第42回日本免疫学会総会
  • Place of Presentation: 幕張メッセ
  • Year and Date: 2013-12-12
• [Presentation] Visualization of Inflammasome activation : monitoring caspase-1 activity in living cells by a genetically-encoded probe SCAT1 (2012)
  • Author(s): 劉霆, 山口良文, 星野克明, 改正恒康, 竹本研, 倉永英里奈, 三浦正幸
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: マリンメッセ福岡
  • Year and Date: 20121211-14
• [Presentation] The Ets transcription factor Spi-B is essential for M-cell differentiation (2012)
  • Author(s): T. Kanaya, K. Hase, T. Kaisho , R. W. Ifor, H Ohno
  • Organizer: 第41回日本免疫学会総会
  • Place of Presentation: 神戸ポートピアホテル
  • Year and Date: 20121205-07
• [Presentation] Spi-B is critical for plasmacytoid dendric cell development in bone marrow (2012)
  • Author(s): I. Sasaki, K. Hoshino, H. Hemmi, M. Sugiyama, T. Yamaguchi, T. Kaisho
  • Organizer: 第41回日本免疫学会総会
  • Place of Presentation: 神戸ポートピアホテル
  • Year and Date: 20121205-07
• [Presentation] Analysis of in vivo function of XC chemokine receptor-expressing dendric cells (2012)
  • Author(s): M. Sugiyama, H. Hemmi, C. Yamazaki, T. Ohta, I. Sasaki, K. Hoshino, T. Kaisho
  • Organizer: 第41回日本免疫学会総会
  • Place of Presentation: 神戸ポートピアホテル
  • Year and Date: 20121205-07
• [Presentation] Long-term memory T cell response induced by adjuvant role of iNKT cells (2012)
  • Author(s): K. Shimizu, M. Asakura, J. Shinga, Y. Sato, K. Hoshino, T.Kaisho , T. Ezaki, S. Fujii
  • Organizer: 第41回日本免疫学会総会
  • Place of Presentation: 神戸ポートピアホテル
  • Year and Date: 20121205-07
• [Presentation] IL-27 affects immune responses via regulation of prostaglandin E2 production by macrophages (2012)
  • Author(s): Y. Sato, S. Suzuki, H. Hara, T. Kaisho , H. Yoshida
  • Organizer: 第41回日本免疫学会総会
  • Place of Presentation: 神戸ポートピアホテル
  • Year and Date: 20121205-07
• [Presentation] A non-synonymous SNP (single nucleotide polymorphism) of PDLIM4 is associated with susceptibility of rheumatoid arthritis and Graves diseases (2012)
  • Author(s): T. Tanaka, Y. Kochi, K. Yamamoto, T. Kaisho
  • Organizer: 第41回日本免疫学会総会
  • Place of Presentation: 神戸ポートピアホテル
  • Year and Date: 20121205-07
• [Presentation] IκB-ζ-deficiency in Epithelial Cells Elicits Sjogren's Syndrome-like Autoimmune Disease (2012)
  • Author(s): A. Okuma, K. Hoshino, T.Kaisho , T. Muta
  • Organizer: 第41回日本免疫学会総会
  • Place of Presentation: 神戸ポートピアホテル
  • Year and Date: 20121205-07
• [Presentation] Evaluation of SCAT1 : a genetically-encoded probe for detecting activation of caspase-1 in living cells (2011)
  • Author(s): K. Shikada, Y. Yamaguchi, T. Liu, K. Takemoto, K. Hoshino, T. Kaisho . E. Kuranaga, M. Miura
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 20111213-16
• [Presentation] HSP70 は PDLIM による NF-κB シグナルの負の制御に必須である (2011)
  • Author(s): 田中貴志, 改正恒康
  • Organizer: 第40回日本免疫学会総会
  • Place of Presentation: 幕張メッセ
  • Year and Date: 20111127-29
• [Presentation] PDLIM4による STAT シグナルの負の制御機構 (2011)
  • Author(s): 平島健志, 改正恒康, 田中貴志
  • Organizer: 第40回日本免疫学会総会
  • Place of Presentation: 幕張メッセ
  • Year and Date: 20111127-29
• [Presentation] 形質細胞様樹状細胞による炎症反応とT細胞免疫応答の制御 (2011)
  • Author(s): H. Takagi, T. Fukaya, Y. Sato, K. Sato, A. Shibazaki, A. Hijikata, O. Ohara, T. Kasiho , B. Malissen, K. Sato
  • Organizer: 第40回日本免疫学会総会
  • Place of Presentation: 幕張メッセ
  • Year and Date: 20111127-29
• [Presentation] Siglec-H による形質細胞様樹状細胞の機能制御 (2011)
  • Author(s): K. Sato, H. Takagi, T. Fukaya, Y. Sato, K. Sato, A. Shibazaki, A. Hijikata, O. Ohara, T. Kasiho , B. Malissen
  • Organizer: 第40回日本免疫学会総会
  • Place of Presentation: 幕張メッセ
  • Year and Date: 20111127-29
• [Presentation] ケモカイン受容体 Xcrl 発現樹状細胞の in vivo における機能的意義 (2011)
  • Author(s): C. Yamazaki, H. Hemmi, R. Miyamoto, I. Sasaki, T. Ito, K. Hoshino, T. Kaisho
  • Organizer: 第40回日本免疫学会総会
  • Place of Presentation: 幕張メッセ
  • Year and Date: 20111127-29
• [Presentation] TLR3を介した乳酸菌2本鎖RNA の IFN-β産生誘導/Double-stranded RNA of lactic acid bacteria triggers TLR3 -mediated IFN-ɤ production by dendritic cells (2011)
  • Author(s): T. Kawashima, H. Yan, Z. Guo, R. Uchiyama, J. Carreras, T. Kaisho , O. Takeuchi, S. Akira, H. Tsutsui, T. Saito, I. Nishimura, N. Tsuji
  • Organizer: 第40回日本免疫学会総会
  • Place of Presentation: 幕張メッセ幕張メッセ
  • Year and Date: 20111127-29
• [Presentation] BDCA3+DC の発現するケモカインレセプター XCR1 と NK 細胞活性化能の解析 (2011)
  • Author(s): 伊藤量基, 宮本理恵, 山崎千尋, 星野克明, 改正恒康, 野村昌作
  • Organizer: 第40回日本免疫学会総会
  • Place of Presentation: 幕張メッセ
  • Year and Date: 20111127-29
• [Presentation] 核酸系免疫アジュバントに対する樹状細胞サブセットの応答機構 (2011)
  • Author(s): 改正恒康
  • Organizer: 第29回日本耳鼻咽喉科免疫アレルギー学会
  • Place of Presentation: 大分
  • Year and Date: 2011-02-10
• [Book] 標準免疫学 (2013)
  • Author(s): 改正恒康
  • Total Pages: 62-69
  • Publisher: 医学書院
• [Book] サイトカインのすべて(完全改訂版) (2012)
  • Author(s): 改正恒康
  • Total Pages: 243-249
  • Publisher: 化学評論社
• [Book] 改正恒康 免疫学 Update- 分子病態の解明と治療への展開 (2012)
  • Author(s): 邊見弘明, 改正恒康
  • Total Pages: 98-106
  • Publisher: 南山堂
• [Book] 免疫の事典 (2011)
  • Author(s): 改正恒康
  • Total Pages: 11, 311, 318
  • Publisher: 朝倉書店
• [Book] Rheumatology(Marc C. Hochberg 他編) (2011)
  • Author(s): T. Kaisho and S. Akira
  • Total Pages: 141-151
  • Publisher: ELSEVIER
• [Book] アジュバント開発研究の新展開 (2011)
  • Author(s): 改正恒康
  • Total Pages: 143-150
  • Publisher: シーエムシー出版
• [Remarks]
  • URL: http://immreg.ifrec.osaka-u.ac.jp/www/