Molecular Basis for the Immune Regulatory Receptor System

2010 Fiscal Year Final Research Report

• Project/Area Number: 20249026
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Immunology
• Research Institution: Tohoku University
• Principal Investigator: TAKAI Toshiyuki Tohoku University, 加齢医学研究所, 教授 (20187917)
• Project Period (FY): 2008 – 2010
• Keywords: 免疫制御 / 受容体 / 自己免疫疾患 / がん / 炎症 / アレルギー

Research Abstract

Paired immunoglobulin-like receptor (PIR)-B, an immunoreceptor tyrosine-based inhibitory motif-harboring receptor for MHC class I molecules, could participate in the regulation of B-1 cells, because PIR-B expression is several times higher in B-1 cells than in B-2 cells or conventional B cells. Recent unexpected findings pointed to a novel inhibitory role of PIR-B in neurite regeneration through binding to three axonal outgrowth inhibitors of myelin including Nogo. Thus, it becomes interesting to determine whether the actions of the inhibitory myelin proteins and MHCI could coexist or be mutually exclusive as to the PIR-B-mediated immune and neural cell inhibition. We studied this subject and obtained data supporting the coexistence of Nogo- and MHCI-mediated inhibition. We now propose a novel mechanism by which PIR-B-mediated regulation is achieved dually via MHCI and Nogo in cells of the immune system.

Research Products

• [Journal Article] Transcriptional activation of the Pirb gene in B cells by PU.1 and Runx3. (2011)
  • Author(s): Arita K, Endo S, Kaifu T, Kitaguchi K, Nakamura A., Ohmori H, Kofu K, Satake M, Takai T.
  • Journal Title: J.Immunol. in press
  • Peer Reviewed
• [Journal Article] Mycobacterial hypersensitivity pneumonitis requires TLR9 - MyD88 in lungCD11b^+CD11c^+ cells. (2011)
  • Author(s): Daito H, Kikuchi T, Sakakibara T, Gomi K, Damayanti T, Zaini J, Tode N, Kanehira M, Koyama S, Fujimura S, Ebina M, Ishii KJ, Akira S, Takai T, Watanabe A, Nukiwa T.
  • Journal Title: Eur.Respir.J. Pages: erj01771-2010. DOI:10.1183/09031936.00177110
  • Peer Reviewed
• [Journal Article] Paired immunoglobulin like receptor-B regulates the suppressive function and fate of myeloid derived suppressor cells. (2011)
  • Author(s): Ma G, Pan PY, Eisenstein S, Divino CM, Lowell C, Takai T, Chen SH
  • Journal Title: Immunity 34 Pages: 385-395(DOI:10.1016/j.immuni.2011.02.004)
  • Peer Reviewed
• [Journal Article] Myelin suppresses axon regeneration by PIR-B/SHP-mediated inhibition of Trk activity. (2011)
  • Author(s): Fujita Y, Endo S, Takai T, Yamashita T.
  • Journal Title: EMBO J. 6;30(7)Epub2011 Mar 1. Pages: 1389-1401
  • Peer Reviewed
• [Journal Article] An immunoreceptor adapter protein, DAP12, suppresses adaptive immune responses mediated by B lymphocytes. (2011)
  • Author(s): Nakano-Yokomizo T, Tahara-Hanaoka S, Nakahashi-Oda C, Nabekura T, Tchao NK, Kadosaki M, Totsuka N, Kurita N, Nakamagoe K, Tamaoka A, Takai T, Yasui T, Kikutani H, Honda S, Shibuya K, Lanier LL, Shibuya A.
  • Journal Title: J.Exp.Med. in press
  • Peer Reviewed
• [Journal Article] Paired immunoglobulin-like receptor B knockout does not enhance axonal regeneration or locomotor recovery after spinal cord injury. (2011)
  • Author(s): Nakamura, Y., Fujita, Y., Ueno, M., Takai, T., Yamashita, T.
  • Journal Title: J.Biol.Chem. 286(3)Epub 2010 Nov 18 Pages: 1876-1883
  • Peer Reviewed
• [Journal Article] Role of PIR-B in Autoimmune Glomerulonephritis.(Review) (2010)
  • Author(s): Takai T, Nakamura A, Endo S.
  • Journal Title: J.Biomed.Biotech. vol.2011 Pages: 275302(doi:10.1155.2011.275302)
  • Peer Reviewed
• [Journal Article] Genetic deletion of paired immunoglobulin-like receptor B does not promote axonal plasticity or functional recovery after traumatic brain injury. (2010)
  • Author(s): Omoto S, Ueno M, Mochio S, Takai T, Yamashita T.
  • Journal Title: J.Neurosci. 30 Pages: 13045-13052
  • Peer Reviewed
• [Journal Article] The inhibitory effects of intravenous administration of rabbit IgG on airway inflammation are dependent on Fcgamma receptor IIb on CD11c+ dendritic cells in murine model. (2010)
  • Author(s): Yamamoto M, Kobayashi K, Ishikawa Y, Nakata K, Funada Y, Kotani Y, Masuda A, Takai T, Azuma T, Yoshida M, Nishimura Y.
  • Journal Title: Clin.Exp.Immunol. 162(2)Epub 2010 Sep 1. Pages: 315-324(doi:10.1111/j.1365-2249.2010.04243.x.)
  • Peer Reviewed
• [Journal Article] TIM1 is an endogenous ligand for LMIR5/CD300b : LMIR5 deficiency ameliorates mouse kidney ischemia/reperfusion injury. (2010)
  • Author(s): Yamanishi Y, Kitaura J, Izawa K, Kaitani A, Komeno Y, Nakamura M, Yamazaki S, Enomoto Y, Oki T, Akiba H, Abe T, Komori T, Morikawa Y, Kiyonari H, Takai T, Okumura K, Kitamura T.
  • Journal Title: J.Exp.Med. 207(7)Epub 2010 Jun 21. Pages: 1501-1511
  • Peer Reviewed
• [Journal Article] The study of allergy by Japanese researchers : a historical perspective. (Review) (2009)
  • Author(s): Takai T, Karasuyama H
  • Journal Title: Int.Immu. 21(12)[Epub ahead of print] Pages: 1311-1316
  • Peer Reviewed
• [Journal Article] Augmented TLR9-induced Btk activation in PIR-B-deficient B-1 cells provokes excessive autoantibody production and autoimmunity. (2009)
  • Author(s): Kubo T, Uchida Y, Watanabe Y, Abe M, Nakamura A, Ono M, Akira S, Takai T.
  • Journal Title: J.Exp.Med. 206 Pages: 1971-1982
  • Peer Reviewed
• [Journal Article] Ectopically expressed PIR-B on T cells constitutively binds to MHC class I and attenuates T helper type 1 responses. (2009)
  • Author(s): Imada M, Masuda M, Satoh R, Ito Y, Goto Y, Matsuoka T, Endo S, Nakamura A, Kawamoto H, Takai T
  • Journal Title: Int.Immu. 21(10) Pages: 1151-1161
  • Peer Reviewed
• [Journal Article] MCSF induces macrophage proliferatin and survival through a DAP12-beta-catenin signaling pathway. (2009)
  • Author(s): Otero K, Turnbull IR, Poliani L, Vermi W, Aoshi T, Takai T, Stanley SL, Miller M, Colonna M.
  • Journal Title: Nat.Immunol. 10(7) Pages: 734-743
  • Peer Reviewed
• [Journal Article] DAP12-independent Ly49H-mediated NK cell responses against mouse cytomegalovirus. (2009)
  • Author(s): Orr MT, Sun JC, Hesslein DG, Arase H, Phillips JH, Takai T, Lanier LL.
  • Journal Title: J.Exp.Med. 206 Pages: 807-817
  • Peer Reviewed
• [Journal Article] Peroxiredoxin III-deficiency sensitizes macrophages to oxidative stress. (2009)
  • Author(s): Li L, Kaifu T, Obinata M, Takai T.
  • Journal Title: J.Biochem. 145(4) Pages: 425-427
  • Peer Reviewed
• [Journal Article] Signal adaptor DAP10 associates with MDL-1 and triggers osteoclastogenesis in cooperation with DAP12. (2009)
  • Author(s): Inui M, Kikuchi Y, Aoki N, Endo S, Maeda T, Sugahara-Tobinai A, Nakamura A, Kumanogoh A, Colonna M, Takai T.
  • Journal Title: Proc Natl Acad Sci USA. 106(12) Pages: 4816-4821
  • Peer Reviewed
• [Journal Article] DAP10 associates with Ly49 receptors but contributes minimally to their expression and function in vivo. (2009)
  • Author(s): Tassi I, Le Friec G, Gilfillan S, Takai T, Yokoyama WM, Colonna M.
  • Journal Title: Eur.J.Immunol. 39(4) Pages: 1129-1135
  • Peer Reviewed
• [Journal Article] Fc receptorγ-chain, a constitutive component of the interleukin-3 receptor, is required for interleukin 3-induced interleukin 4 production in basophils. (2009)
  • Author(s): Hida S, Yamasaki S, Sakamoto Y, Takamoto M, Obata K, Takai T, Karasuyama H, Sugane K, Saito T, Taki S.
  • Journal Title: Nat.Immunol. 10(2) Pages: 214-222
  • Peer Reviewed
• [Journal Article] Essential role of DAP12 signaling in macrophage programming into a fusion-competent state. (2008)
  • Author(s): Helming L, Tomasello E, Kyriakides TR, Martinez FO, Takai T, Gordon S, Vivier E.
  • Journal Title: Sci Signal. 1(43)
  • Peer Reviewed
• [Journal Article] Regulation of cytotoxic T lymphocyte triggering by PIR-B on dendritic cells. (2008)
  • Author(s): Endo S, Sakamoto Y, Nakamura A, Takai T.
  • Journal Title: Proc.Natl.Acad.Sci.USA 105 Pages: 14515-14520
  • Peer Reviewed
• [Journal Article] Inhibitory immunoglobulin-like receptors LILRB and PIR-B negatively regulate osteoclast development. (2008)
  • Author(s): Mori Y, Tsuji S, Inui M, Sakamoto Y, Endo S, Ito Y, Fujimura S, Koga T, Nakamura A, Takayanagi H, Itoi E, Takai T.
  • Journal Title: J.Immunol. 181(7) Pages: 4742-4751
  • Peer Reviewed
• [Journal Article] PIR-B-deficient mice are susceptible to Salmonella infection. (2008)
  • Author(s): Torii I, Oka S, Hotomi M, Benjamin WH Jr, Takai T, Kearney JF, Briles DE, Kubagawa H.
  • Journal Title: J.Immunol. 181(6) Pages: 4229-4239
  • Peer Reviewed
• [Journal Article] A novel regulatory role of gp49B on dendritic cells in T cell priming. (2008)
  • Author(s): Kasai S, Inui M, Nakamura K, Kakizaki Y, Endo S, Nakamura A, Ito S, Takai T.
  • Journal Title: Eur.J.Immunol. 38 Pages: 2426-2437
  • Peer Reviewed
• [Journal Article] Comparison of 30 immunity-related genes from thecommon marmoset with orthologues from human and mouse. (2008)
  • Author(s): Kohu K, Yamabe E, Matsuzawa A, Onda D, Suemizu H, Sasaki E, Tanioka Y, Yagita H, Suzuki D, Kametani Y, Takai T, Toyoda A, Habu S, Satake M.
  • Journal Title: Tohoku J.Exp.Med. 215 Pages: 167-180
  • Peer Reviewed
• [Journal Article] Fcγ Receptor Regulation of Citrobacter rodentium Infection. (2008)
  • Author(s): Masuda A, Yoshida M, Shiomi H, Ikezawa S, Takagawa T, Tanaka H, Chinzei R, Ishida T, Morita Y, Kutsumi H, Inokuchi H, Wang S, Kobayashi K, Mizuno S, Nakamura A, Takai T, Blumberg RS, Azuma T.
  • Journal Title: Infect.Immunity 76 Pages: 1728-1737
  • Peer Reviewed
• [Journal Article] Tyrosine kinases Btk and Tec regulate osteoclast differentiation by linking RANK and ITAM signals. (2008)
  • Author(s): Shinohara M, Koga T, Okamoto K, Sakaguchi S, Arai K, Yasuda H, Takai T, Kodama T, Morio T, Geha RS, Kitamura D, Kurosaki T, Ellmeier W, Takayanagi H.
  • Journal Title: Cell 132(5) Pages: 794-806
  • Peer Reviewed
• [Journal Article] Analysis of mouse LMIR5/CLM7 as an activating receptor: differential regulation of LMIR5/CLM7 in ouse versus human cells. (2008)
  • Author(s): Yamanishi Y, Kitaura J, Izawa K, Matsuoka T, Oki T, Lu Y, Shibata F, Yamazaki S, Kumagai H, Nakajima H, Maeda-Yamamoto M, Tybulewicz VLJ, Takai T, Kitamura T.
  • Journal Title: Blood 111 Pages: 688-698
  • Peer Reviewed
• [Presentation] 免疫制御受容体PIR-Bによる自己免疫の制御 (2011)
  • Author(s): 高井俊行
  • Organizer: 第2回愛媛大学プロテオ医学研究センターシンポジウム(招待講演)
  • Place of Presentation: 愛媛
  • Year and Date: 2011-02-06
• [Presentation] (Invited) : Regulation of TLR9 activation and autoantibody production in B-1 cells by PIR-B, an MHC class I receptor. (2010)
  • Author(s): 高井俊行
  • Organizer: 8th German-Japanese Symposium.
  • Place of Presentation: Hotel Strandperle, Cuxhaven, Germany
  • Year and Date: 20100926-20100929
• [Presentation] (Invited) : Regulation of autoimmunity by PIR-B. (2010)
  • Author(s): 高井俊行
  • Organizer: Asian Aging Core for Longevity, 2010
  • Place of Presentation: Neighborhood Hotel in Jeju, Jeju Island, Korea
  • Year and Date: 20100822-20100824
• [Presentation] (2010)
  • Author(s): 高井俊行
  • Organizer: 免疫制御受容体による自己抗体の産生制御(招待講演)株式会社ベネシス
  • Place of Presentation: 大阪
  • Year and Date: 2010-12-13
• [Presentation] Kinetic analysis of the association between PIR-B and its related molecules in B cells. (2010)
  • Author(s): Y.Sakamoto, Y.Watanabe, A.Nakamura, T.Takai.
  • Organizer: 14th International Congress of Immunology (Kobe)(ポスター発表[PP-052-15])
  • Year and Date: 2010-08-25
• [Presentation] A regulatory role of PIR-B in plasmacytoid dendritic cells (2010)
  • Author(s): Y.Mitsuhashi, A.Nakamura, T.Nukiwa, T.Takai.
  • Organizer: 14th International Congress of Immunology (Kobe)(ポスター発表[PP-095-15])
  • Year and Date: 2010-08-25
• [Presentation] 自己免疫疾患におけるIVIG療法の作用機序の最新知見 (2010)
  • Author(s): 高井俊行
  • Organizer: 献血ベニロン-I発売30周年記念講演会(招待講演)
  • Place of Presentation: 帝国ホテル 東京
  • Year and Date: 2010-07-10
• [Presentation] A regulatory role of PIR-B in plasmacytoid dendritic cells (2010)
  • Author(s): Nakamura A, Mitsuhashi M, Takai T
  • Organizer: The 5th International Symposium of Institute Network
  • Place of Presentation: Kanazawa
  • Year and Date: 2010-06-24
• [Presentation] 自己免疫疾患におけるIVIG療法の作用機序の最新知見 (2010)
  • Author(s): 高井俊行
  • Organizer: 献血ベニロン-I発売30周年記念講演会(招待講演)
  • Place of Presentation: ヒルトンホテル大阪 大阪
  • Year and Date: 2010-06-19
• [Presentation] 抑制性受容体による免疫制御機構の解析 (2010)
  • Author(s): 高井俊行
  • Organizer: 日本薬学会第130年会(招待講演)
  • Place of Presentation: 岡山
  • Year and Date: 2010-03-28
• [Presentation] 免疫抑制性レセプターPIR-Bによるアレルギー制御 (2009)
  • Author(s): 高井俊行, 中村晃
  • Organizer: 第59回日本アレルギー学会秋季学術大会
  • Place of Presentation: 秋田市
  • Year and Date: 2009-10-29
• [Presentation] (Invited Speaker and Chair of the session Track 6-3) : Regulation of cytotoxic T lymphocyte triggering by PIR-B on dendritic cells. (2009)
  • Author(s): 高井俊行
  • Organizer: In : Tumor Immunology and Immunotherapy. 2009 4th Medical Biotech Forum
  • Place of Presentation: Dalian, China
  • Year and Date: 2009-08-10
• [Presentation] Rheumatoid Factor (RF) Production Is Regulated by PIR-B on B-1 Cells and its Excessive Elevation Can Link to Autoimmunity. (2009)
  • Author(s): Toshiyuki Takai, Tomohiro Kubo, Yuki Uchida, Yuko Watanabe, Masahiro Abe, Akira Nakamura
  • Organizer: BIT's I^<st> Annual International Congress of Antibody-2009
  • Place of Presentation: Beijing, China
  • Year and Date: 2009-05-22
• [Presentation] Augmented TLR9-induced Btk activation in PIR-B-deficient B-1 cells provokes excessive rheumatoid factor production and autoimmunity. (2009)
  • Author(s): 高井俊行
  • Organizer: BIT's Life Sciences' 2nd Annual Protein and Peptide Conference (PepCon 2009))
  • Place of Presentation: Seoul, South Korea
  • Year and Date: 2009-04-03
• [Book] Adv Exp Med Biol.640(Fc receptor targeting in the treatment of allergy, autoimmune diseases and cancer.) (2008)
  • Author(s): Nakamura A, Kubo T, Takai T
  • Total Pages: 220-233
• [Remarks] ホームページ等
  • URL: http://www.idac.tohoku.ac.jp/dep/expimu/