Roles of guidance factors in immune regulation

2012 Fiscal Year Final Research Report

• 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
• 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

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.

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) Pages: 200-9
  • DOI: 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) Pages: 21022-7
  • DOI: 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) Pages: 314-25
  • DOI: doi:10.1016/j.immuni.2012.05.026
  • 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) Pages: 594-600
  • DOI: 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) Pages: 1499-506
  • DOI: doi:10.4049/jimmunol.0903302
  • 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) Pages: 1-11
  • DOI: doi:10.1007/s10875-008-9263-7.
  • 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) Pages: 3935-40
  • DOI: 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) Pages: 251-62
  • DOI: 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) Pages: 695-708
  • DOI: doi:10.1093/intimm/dxn029.
  • Peer Reviewed
• [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
  • Year and Date: 20120911-14
• [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.
  • Year and Date: 20120801-04
• [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.
  • Year and Date: 20120302-06
• [Presentation] Semaphorins in immune cell communication. (2010)
  • Author(s): Kikutani, H
  • Organizer: 14th International Congress of Immunology
  • Place of Presentation: Kobe, Japan
  • Year and Date: 20100822-27
• [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.
  • Year and Date: 20100311-13
• [Presentation] Semaphorins and inflammatory resonses. (2009)
  • Author(s): Kikutani, H.
  • Organizer: EMBO Workshop "Semaphorin Function & Mechanisms of Actioni"
  • Place of Presentation: Cernay, France
  • Year and Date: 20090508-11
• [Remarks]
  • URL: http://www.biken.osaka-u.ac.jp/biken/mol-imm/Molecular_Immunology/Welcome.html