Roles of guidance factors in immune regulation

• Project/Area Number: 20229007
• Research Category: Grant-in-Aid for Scientific Research (S)
• Allocation Type: Single-year Grants
• Research Field: Immunology
• Research Institution: Osaka University
• Principal Investigator: KIKUTANI Hitoshi 大阪大学, 微生物病研究所, 教授 (80161412)
• Co-Investigator(Kenkyū-buntansha): YASUI Teruhito 大阪大学, 微生物病研究所, 准教授 (60283074) ; MIZUI Masayuki 大阪大学, 微生物病研究所, 助教 (30423106) ; SAKAKIBARA Shuhei 大阪大学, 微生物病研究所, 助教 (10618838)
• Project Period (FY): 2008 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥207,090,000 (Direct Cost: ¥159,300,000、Indirect Cost: ¥47,790,000); Fiscal Year 2012: ¥36,400,000 (Direct Cost: ¥28,000,000、Indirect Cost: ¥8,400,000); Fiscal Year 2011: ¥36,400,000 (Direct Cost: ¥28,000,000、Indirect Cost: ¥8,400,000); Fiscal Year 2010: ¥36,400,000 (Direct Cost: ¥28,000,000、Indirect Cost: ¥8,400,000); Fiscal Year 2009: ¥36,400,000 (Direct Cost: ¥28,000,000、Indirect Cost: ¥8,400,000); Fiscal Year 2008: ¥61,490,000 (Direct Cost: ¥47,300,000、Indirect Cost: ¥14,190,000)
• Keywords: セマフォリン / プレキシン / アレルギー疾患 / T細胞 / B細胞 / 樹状細胞 / Sema4D / plexin B2 / Akt / PKN1 / B細胞抗原受容体 / EBウイルス / Sema4A / Tim-2 / Th2 / IL-4 / リンパ球 / 免疫制御 / Plexin / セマフォリンファミリー / 分子標的 / 気道アレルギー

Research Abstract

This study has been carried out to determine roles of semaphorins and their receptors in immune regulation. We showed that Sema4A and Sema3A play roles in negative regulation in allergic immune responses and in trafficking of dendritic cells from the periphery to lymph nodes, respectively. Tim-4 was also shown to play a regulatory role in T-cell mediated immunity. Furthermore, PKN1, a serine-threonine kinase, whose functions had been unknown, turned out to be necessary not only for regulation of B cell antigen receptor signals and but also for selection of high affinity antibody producing B cells.

Assessment Rating

Verification Result (Rating)

A-

Research Products

• [Journal Article] Morihana T, Goya S, Mizui M, Yasui T, Prasad DV, Kumanogoh A, Tamura M, Shikina T, Maeda Y, Iwamoto Y, Inohara H, Kikutani H. (2013)
  • Author(s): An inhibitory role for Sema4A in antigen-specific allergic asthma
  • Journal Title: J Clin Immunol. Volume: 33(1) Issue: 1 Pages: 200-9
  • DOI: 10.1007/s10875-012-9798-5
  • Peer Reviewed
• [Journal Article] Protein kinase N1, a cell inhibitor of Akt kinase, has a central role in quality control of germinal center formation (2012)
  • Author(s): Yasui T, Sakakibara-Yada K, Nishimura T, Morita K, Tada S, Mosialos G, Kieff E, Kikutani H
  • Journal Title: Proc Natl Acad Sci U S A Volume: 109(51) Issue: 51 Pages: 21022-7
  • DOI: 10.1073/pnas.1218925110
  • Peer Reviewed
• [Journal Article] The CD100 receptor interacts with its plexin B2 ligand to regulate epidermal Y^δ T cell function. (2012)
  • Author(s): Witherden DA, Watanabe M, Garijo O, Rieder SE, Sarkisyan G, Cronin SJ, Verdino P, Wilson IA, umanogoh A, Kikutani H, Teyton L, Fischer WH, Havran WL
  • Journal Title: Immunity. Volume: 37(2) Issue: 2 Pages: 314-25
  • DOI: 10.1016/j.immuni.2012.05.026
  • Peer Reviewed
• [Journal Article] The immunoreceptor adapter protein DAP12 suppresses B lymphocyte-driven adaptive immune responses (2012)
  • Author(s): Nakano-Yokomizo, T.
  • Journal Title: J.Exp.Med. Volume: 208 Pages: 1661-1671
  • Peer Reviewed
• [Journal Article] Semaphorin 4C and 4G are ligands of Plexin-B2 required in cerebellar development. (2011)
  • Author(s): Maier, V., et al.
  • Journal Title: Mol.Cell.Neurosci. Volume: 46 Pages: 419-431
  • Peer Reviewed
• [Journal Article] Semaphorins guide the entry of dendritic cells into the lymphatics by activating myosin II (2010)
  • Author(s): Takamatsu H, Takegahara N, Nakagawa Y, Tomura M, Taniguchi M, Friedel RH, Rayburn H, Tessier-Lavigne M, Yoshida Y, Okuno T, Mizui M, Kang S, Nojima S, Tsujimura T, Nakatsuji Y, Katayama I, Toyofuku T, Kikutani H, Kumanogoh A
  • Journal Title: Nat Immunol. Volume: 11(7) Issue: 7 Pages: 594-600
  • DOI: 10.1038/ni.1885
  • Peer Reviewed
• [Journal Article] Roles of Sema4D-plexin-B1 interactions in the central nervous system for pathogenesis of experimental autoimmune encephalomyelitis. (2010)
  • Author(s): Okuno T, Nakatsuji Y, Moriya M, Takamatsu H, Nojima S, Takegahara N, Toyofuku T, Nakagawa Y, Kang S, Friedel RH, Sakoda S, Kikutani H, Kumanogoh A
  • Journal Title: J Immunol. Volume: 184(3) Issue: 3 Pages: 1499-506
  • DOI: 10.4049/jimmunol.0903302
  • Peer Reviewed
• [Journal Article] Semaphorins guide cells into the lymphatics by activating myosin II. (2010)
  • Author(s): Takamatsu, H., N.Takegahara, Y.Nakagawa, M.Tomura, M.Taniguchi, R.H.Friedel, H.Rayburn, M.Tessier-Lavigne, Y.Yoshida, T.Okuno, M.Mizui, S.Kang, S.Nojima, T.Tsujimura, Y. Nakatsuji, I.Katayama, T.Toyofuku, H.Kikutani, A.Kumanogoh.
  • Journal Title: Nat Immunol 11 Pages: 594-600
  • Peer Reviewed
• [Journal Article] Semaphorins guide the entry of dendritic cells into the lymphatics by activating myosin II. (2010)
  • Author(s): Takamatsu, H., et al.
  • Journal Title: Nat Immunol. Volume: 11 Pages: 594-600
  • Peer Reviewed
• [Journal Article] Deletion of Sema4D gene reduces intimal neovascularization and plaque growth in apolipoprotein E-deficient mice. (2010)
  • Author(s): Yukawa, et al.
  • Journal Title: Int.J.Mol.Med. Volume: 26 Pages: 39-44
  • Peer Reviewed
• [Journal Article] Critical role of IкB Kinase α in TLR7/9-induced type I IFN production by conveneional dentritic cells. (2010)
  • Author(s): Hoshino, H., et al.
  • Journal Title: J.Immunol. in press
  • Peer Reviewed
• [Journal Article] Immune semaphorins: novel features of neural guidance molecules. (2009)
  • Author(s): Mizui M, Kumanogoh A, Kikutani H.
  • Journal Title: J Clin Immunol. Volume: 29(1) Issue: 1 Pages: 1-11
  • DOI: 10.1007/s10875-008-9263-7
  • Peer Reviewed
• [Journal Article] Immune semaphorins : novel features of neural guidance molecules. (2009)
  • Author(s): Mizui, M., A.Kuanogoh, H. Kikutani
  • Journal Title: J.Clin.Immunol. 29 Pages: 1-11
  • Peer Reviewed
• [Journal Article] Enhanced humoral immune responses against T-independent antigens in Fcα/μR-deficient mice. (2009)
  • Author(s): Honda, S.I., et al.
  • Journal Title: Proc.Natl.Aca.Sci., USA, 106 Pages: 11230-11235
  • Peer Reviewed
• [Journal Article] Immune semaphorins : novel features of neural guidance molecules. (2009)
  • Author(s): Mizui, M., et al.
  • Journal Title: J. Celin. Immunol., 29:1-11, 2009 29 Pages: 1-11
  • Peer Reviewed
• [Journal Article] Involvement of Sema4A in the progression of experimental autoimmune myocarditis. (2008)
  • Author(s): Makino N, Toyofuku T, Takegahara N, Takamatsu H, Okuno T, Nakagawa Y, Kang S, Nojima S, Hori M, Kikutani H, Kumanogoh A.
  • Journal Title: FEBS Lett Volume: 582(28) Issue: 28 Pages: 3935-40
  • DOI: 10.1016/j.febslet.2008.10.040
  • Peer Reviewed
• [Journal Article] Repulsive and attractive semaphorins cooperate to direct the navigation of cardiac neural crest cells. (2008)
  • Author(s): Toyofuku T, Yoshida J, Sugimoto T, Yamamoto M, Makino N, Takamatsu H, Takegahara N, Suto F, Hori M, Fujisawa H, Kumanogoh A, Kikutani H.
  • Journal Title: Dev Biol Volume: 321(1) Issue: 1 Pages: 251-62
  • DOI: 10.1016/j.ydbio.2008.06.028
  • Peer Reviewed
• [Journal Article] Bimodal regulation of T cell-mediated immune responses by TIM-4. (2008)
  • Author(s): Mizui M, Shikina T, Arase H, Suzuki K, Yasui T, Rennert PD, Kumanogoh A, Kikutani H.
  • Journal Title: Int Immunol. Volume: 20(5) Issue: 5 Pages: 695-708
  • DOI: 10.1093/intimm/dxn029
  • NAID: 10021241281
  • Peer Reviewed
• [Journal Article] Repulsive and attractive semaphorins cooperate to direct the navigation of cardiac neural crest cells. (2008)
  • Author(s): Toyofuku, T.,J.Yoshida, T.Sugimoto, M.Yamamoto, N.Makino, H.Takamatsu, N.Takegahara, F.Suto, M.Hori, H.Fujisawa, A.Kumanogoh, H.Kikutani
  • Journal Title: Dev.Biol. 321 Pages: 251-262
  • Peer Reviewed
• [Journal Article] Bimodal regulation of T cell-mediated immune responses by TIM-4. (2008)
  • Author(s): Mizui, M., T.Shikina, H.Arase, K.Suzuki, T.Yasui, P.D.Rennert, A.Kumanogoh, H.Kikutani
  • Journal Title: Int.Immunol. 20 Pages: 695-708
  • NAID: 10021241281
• [Journal Article] Bimodal regulation of T cell-mediated immune responses by TIM-4 (2008)
  • Author(s): Mizui, M., et al.
  • Journal Title: Int. Immunol., 20:695-708 20 Pages: 695-708
  • NAID: 10021241281
  • Peer Reviewed
• [Journal Article] Neuropilin-1 : the glue between regulatory T cells and dendritic cells?, 28 : 302-303, 2008. (2008)
  • Author(s): Mizui, M., H. Kikutani
  • Journal Title: Immunity 28 Pages: 302-303
  • Peer Reviewed
• [Presentation] Novel endogenous regulator of Th2 inflammation : Semaphorins (2012)
  • Author(s): 菊谷仁
  • Organizer: 2012 Annual Meeting of American Academy of Allergy Asthma & Immunology
  • Place of Presentation: Orlando, Florida, USA(招待講演)
  • Year and Date: 2012-03-02
• [Presentation] Pathogenic activation and evasion of humoral immune responses by γ-herpesvirus infection (2012)
  • Author(s): Yasui, T
  • Organizer: The 11thAwaji International Forum on Infection and Immunity.
  • Place of Presentation: Awaji, Hyogo, Japan
• [Presentation] Expression of EB virus LMP2a modifies the selection of B cells in germinal center. (2012)
  • Author(s): Minamitani, T., T. Yasui, and H. Kikutani.
  • Organizer: International Congress on Oncogenic Herpesviruses and Associated Diseases
  • Place of Presentation: Philadelphia, Pennsylvania, USA.
• [Presentation] Novel endogenous regulator of Th2 inflammation: Semaphorins (2012)
  • Author(s): Kikutani, H.
  • Organizer: 2012 Annual Meeting of American Academy of Allergy Asthma & Immunology
  • Place of Presentation: Orlando, Florida, USA.
• [Presentation] Inhibition of germinal center formation and humoral immune responses by EB virus protein LMP1 (2012)
  • Author(s): Tsai, Chiau-Yuang
  • Organizer: 第41回日本免疫学会
  • Place of Presentation: 神戸市
• [Presentation] Epstein-barr virus LMP2a affects affinity maturation but not germina. (2012)
  • Author(s): Minamitan, T.
  • Organizer: 第41回日本免疫学会
  • Place of Presentation: 神戸市
• [Presentation] Generation and selection of virus- and self-reactive B cells during herpesvirus infection. (2012)
  • Author(s): Sakakibara, S.
  • Organizer: 第41回日本免疫学会
  • Place of Presentation: 神戸市
• [Presentation] Population analysis of effector CD4+ T cells in MHV68 infection by single cell-based RT-PCR. (2012)
  • Author(s): Morita, K.
  • Organizer: 第41回日本免疫学会
  • Place of Presentation: 神戸市
• [Presentation] ガンマヘルペスウイルス感染による自己抗原産生 (2012)
  • Author(s): 榊原修平
  • Organizer: 第60回日本ウイルス学会
  • Place of Presentation: 大阪市
• [Presentation] Pathogenic activation and evasion of humoral immune responses by γ-herpesvirus infection. (2012)
  • Author(s): Yasui, T.
  • Organizer: The 11th Awaji International Forum on Infection and Immunity
  • Place of Presentation: 淡路市
  • Invited
• [Presentation] Population analysis of effector CD4+ T cells in MHV68 infection by single cell-based RT-PCR. (2012)
  • Author(s): Morita, K.
  • Organizer: The 11th Awaji International Forum on Infection and Immunity
  • Place of Presentation: 淡路市
• [Presentation] Generation of virus-and self-reactive B cells during herpesvirus infection. (2012)
  • Author(s): Sakakibara, S.
  • Organizer: The 11th Awaji International Forum on Infection and Immunity
  • Place of Presentation: 淡路市
• [Presentation] Expression of EB virus LMP2a modifies the selection of B cells in germinal center. (2012)
  • Author(s): Minamitani, T.
  • Organizer: International Congress on Oncogenic Herpesviruses and Associated Diseases.
  • Place of Presentation: Philadelphia, USA
• [Presentation] ガンマヘルペスウイルス感染による免疫関連疾患発症機構の解明 (2012)
  • Author(s): 榊原修平
  • Organizer: 第27回ヘルペスウイルス研究会
  • Place of Presentation: 愛知県知多郡東浦町
• [Presentation] Epstein-BarrウイルスLatent membrane protein 2Aは抗原特異的B細胞の選択的除去によってウイルス感染成立に寄与している (2012)
  • Author(s): 南谷武春
  • Organizer: 第27回ヘルペスウイルス研究会
  • Place of Presentation: 愛知県知多郡東浦町
• [Presentation] EBウイルスLMP1は関連腫瘍発生の必要十分分子となり得るか？－胚中心B細胞特異的LMP1発現マウスの解析 (2012)
  • Author(s): 安居輝人
  • Organizer: 第27回ヘルペスウイルス研究会
  • Place of Presentation: 愛知県知多郡東浦町
• [Presentation] Semaphorins in immune cell communication. (2010)
  • Author(s): 菊谷仁
  • Organizer: 14^<th> International Congress of Immunology
  • Place of Presentation: 兵庫県・神戸国際展示場(招待講演)
  • Year and Date: 2010-08-27
• [Presentation] A role of protein kinase N1 in qualilty control of germinal center Bcells. (2010)
  • Author(s): 菊谷仁
  • Organizer: 9^<th> International Conference on Human Lyukocyte Differentiation Antigen.
  • Place of Presentation: Barcelona, Spain
  • Year and Date: 2010-03-12
• [Presentation] A role of protein kinase N1 in quality control of germinal center B cells. (2010)
  • Author(s): Kikutani, H.
  • Organizer: 9th International Conference on Human Leukocyte Differentiation Antigen
  • Place of Presentation: Barcelona, Spain.
• [Presentation] Semaphorins in immune cell communication. (2010)
  • Author(s): Kikutani, H
  • Organizer: 14th International Congress of Immunology
  • Place of Presentation: Kobe, Japan
• [Presentation] Semaphorins in immune cell communication. (2010)
  • Author(s): Kikutani, H.
  • Organizer: 14^<th> International Congress of Immunology
  • Place of Presentation: Kobe, Japan.
• [Presentation] A role of protein kinase N1 in quality control of germinal center B cells. (2010)
  • Author(s): Kikutani, H.
  • Organizer: 9^<th> International Conference on Human Leukocyte Differentiation Antigen.
  • Place of Presentation: Barcelona, Spain.
• [Presentation] Comprehensive detection assay of physiological interaction partners for the Epstein-Barr virus latent membrane protein 1 by bimolecular fluorescence complementation system coupled with enhanced retrovirus mutagenesis. (2010)
  • Author(s): Mizui, M., T.Yasui, K.Morita, T.Morimoto, S.Tada, H.Kikutani
  • Organizer: The 14^<th> Biennial Conference of the International Association for Research on Epstein-Barr Virus and Associated Diseases.
  • Place of Presentation: Birmingham, UK.
• [Presentation] Semaphorins and inflammatory resonses. (2009)
  • Author(s): Kikutani, H.
  • Organizer: EMBO Workshop "Semaphorin Function & Mechanisms of Actioni"
  • Place of Presentation: Cernay, France
• [Presentation] Semaphorins and inflammatory resonses. (2008)
  • Author(s): Kikutani, H.
  • Organizer: EMBO Workshop "Semaphorin Function & Mechanisms of Action"
  • Place of Presentation: Cernay, France
• [Presentation] EBウイルス関連腫瘍の発症メカニズム‐胚中心B細胞特異的LMP1発現マウスの解析
  • Author(s): 安居輝人
  • Organizer: 第9回EBウイルス研究会
  • Place of Presentation: 米子市
• [Remarks]
  • URL: http://www.biken.osaka-u.ac.jp/biken/mol-imm/Molecular_Immunology/Welcome.html
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  • URL: http://www.biken.osaka-u.ac.jp/
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  • URL: http://www.biken.osaka-u.ac.jp/act/act_kikutani.php