Institute of Development, Aging and Cancer, Tohoku University


Department of Experimental Immunology

Professor Toshiyuki TAKAI, PhD
Senior Assistant Professor Masanori INUI, PhD
Guest Instructor Akira NAKAMURA, MD, PhD (Kanazawa Medical University)
Guest Instructor Motoko MORIMOTO, DVM, PhD (Miyagi University)
Guest Instructor Yuzuru SAKAMOTO, PhD (Tohoku Institute of Technology)
Assistant Professor Ari Itoh-Nakadai, PhD
Technical Assistant Akiko TOBINAI
Secretarial Assistant Takako NAKAMURA
Homepage of This Laboratory

Lab Research Focus: Immunoregulation by Immunoglobulin-Like Receptors (IgLRs)
FcR-Mediated Immunoregulation Humoral and cellular immune responses communicate each other via Fc receptors (FcRs) expressed on various hematopoietic cells (Fig. 1). Recent studies on several FcR knockout mice demonstrated pivotal roles of an IgG/FcγR system in the regulation of immune responses and the onset of hypersensitivity. The g subunit of FcRs is an essential component of the complex, and is required for both receptor assembly and signal transduction. FcR γ chain-deficient mice have lost the functional expression of FcεRI, FcγRI, and FcγRIII, and have been unable to mount several types of hypersensitive reactions including IgE-dependent anaphylaxis. In contrast, FcγRIIB-deficient mice exhibit the augmented humoral immune responses, IgG-mediated anaphylaxis reaction, and exacerbated autoimmune diseases. Thus, the regulatory system of murine hypersensitive responses involves both positive and negative control through FcRs. Elucidation of the detailed cascades of the regulatory system by FcRs as well as by several novel groups of potent inhibitory or stimulatory receptors should be valuable to develop novel therapeutic procedures for allergic and autoimmune disorders, and cancer, as well as for successful tissue transplantation. These novel groups of activating and inhibitory receptor pairs are now collectively termed as immunoglobulin-like receptors (IgLRs).

Physiological Role of PIR. We have cloned p91 from mouse splenocytes in the course of attempts to fish out possible murine homologs of human FcαRI. P91, which is now termed PIR-B, constitutes a unique murine IgLR family. The structural features of PIR and the chromosomal location of their genes support the notion that the PIR family is homologous to the LILR family rather than the FcγRs in man and mouse (Fig. 2). We have generated PIR-B knockout mice, and found that the mutant mice are prone to mount Th2-type immune responses due to immature dendritic cells. Also, we have found that PIR-A/B bind to MHC class I molecules as their ligands. On the other hand, B cells are divided into two fractions, B-2 cells that produce antigen-specific antibodies, and B-1 cells that produce non-specific natural antibodies (Fig. 3). Recently, we have found the B-1 cells lacking PIR-B produced a higher amount of rheumatoid factor (RF) by stimulation with Toll-like receptor (TLR) 9, showing that PIR-B regulates autoimmunity by the regulation of TLR9 signaling (Fig. 4).

Very recently, other groups demonstrated that PIR-B also binds to myelin- associated glycoproteins that inhibit axonal generation, suggesting that PIR-B regulates various biological responses as well as immune systems. We are developing the research for overcoming immune diseases through the investigation of physiological roles of inhibitory receptors, such as FcγRIIB and PIR-B.

Fig. 1. Schematic representation of Fc receptors (FcRs) in humans and mice.
An inhibitory FcR, FcγRIIB bears immunoreceptor tyrosine-based inhibitory motifs (ITIMs) in its cytoplasm, whereas activating FcRs associate with FcRγ-chain that contains immunoreceptor tyrosine-based activation motifs (ITAMs) in its cytoplasm.
Fig. 2. Schematic representation of MHC class I-binding receptors.
PIR (Paired immunoglobulin-like receptor)-B, and human PIR-B relatives, Leukocyte immunoglobulin-like receptor (LILR)Bs, bear ITIMs, and deliver inhibitory signaling into immune cells. PIR-A and LILRAs function as activating receptors through the association with FcRγ-chain.
Fig. 3. B-1 and B-2 cell differentiation. B-2 cells, but not B-1 cells, are negatively selected when encounter autoantigens.
Fig. 4. A regulatory mechanism of PIR-B on Toll-like receptor (TLR) 9-mediated rheumatoid factor (RF) production by B-1 cells. PIR-B on B-1 cells suppresses TLR9 signaling via Bruton’s tyrosine kinase (Btk) dephosphorylation, which leads to attenuated activation of NF-kB p65RelA, and blocks the production of RF.

Publication list (2000-)

169. Inui M, Tazawa K, Kishi Y, Takai T. Platelets convert peripheral blood circulating monocytes to regulatory cells via immunoglobulin G and activating-type Fcg receptors.BMC Immunol. in press.
168. Kimura T, Endo S, Inui M, Saitoh S-i, Miyake K, Takai T. Endoplasmic protein Nogo-B (RTN4-B) interacts with GRAMD4 and regulates TLR9-mediated innate immune responses. J. Immunol. in press.
167. Inui M*, Hirota S*, Hirano K, Fujii H, Sugahara-Tobinai A, Ishii T, Harigae H, Takai T. (*equal contribution) Human CD43+ B cells are closely related not only to memory B cells phenotypically but also to plasmablasts developmentally in healthy individuals. Int Immunol. 2015 Mar 5. pii: dxv009.
166. Nehishi–Koga T, Gober HJ, Sumiya E, Komatsu N, Okamoto K, Sawa S, Suematsu S, Suda T, Sato K, Takai T, Takayanagi H. Immune complexes regulate bone metabolism through FcRγ signaling. Nat Commun in press.
165. Kobayashi M, Konishi H, Takai T, Kiyama H. A DAP12-Dependent Signal Promotes Pro-Inflammatory Polarization in Microglia Following Nerve Injury and Exacerbates Degeneration of Injured Neurons Glia in press.
164. Kanno A, Tanimura N, Ishizaki M, Ohko K, Motoi Y, Onji M, Fukui R, Shimozato T, Yamamoto K, Shibata T, Sano S, Sugahara-Tobinai A, Takai T, Ohto U, Shimizu T, Saitoh S, Miyake K. Targeting cell surface TLR7 for therapeutic intervention in autoimmune diseases. Nat Commun in press.
163. Kanari Y, Sugahara–Tobinai A, Takahashi H, Inui M, Nakamura A, Hirose S, Takai T.
Dichotomy in the FcγRIIB deficiency and autoimmune-prone SLAM haplotype clarifies the roles of the Fc receptor in development of autoantibodies and glomerulonephritis. BMC Immunol 2014, 15:47  doi:10.1186/s12865-014-0047-y
162. Fukao S, Haniuda K, Nojima T, Takai T, Kitamura D. Gp49B-Mediated Negative Regulation of Antibody Production by Memory and Marginal Zone B Cells. J Immunol. 2014 Jul 15;193(2):635-44. doi: 10.4049/jimmunol.1302772.
161. Yasukawa S, Miyazaki Y, Yoshii C, Nakaya M, Ozaki N, Toda S, Kuroda E, Ishibashi K, Yasuda T, Natsuaki Y, Mi-ichi F, Iizasa E, Nakahara T, Yamazaki M, Kabashima K, Iwakura Y, Takai T, Saito T, Kurosaki T, Malissen B, Ohno N, Furue M, Yoshida H, Hara H. An ITAM-Syk-CARD9 signalling axis triggers contact hypersensitivity by stimulating IL-1 production in dendritic cells. Nat Commun 2014 5:3755. doi: 10.1038/ncomms4755.
160. Lo TH, Tseng KY, Tsao WS, Yang CY, Hsieh SL, Chiu AW, Takai T, Mak TW, Tarng DC, Chen NJ. TREM-1 regulates macrophage polarization in ureteral obstruction. Kidney Int. 2014; 86(6):1174-86. doi: 10.1038/ki.2014.205.
159. Kam TI, Song S, Gwon Y, Park H, Yan JJ, Im I, Choi JW, Choi TY, Kim J, Song DK, Takai T, Kim YC, Kim KS, Choi SY, Choi S, Klein WL, Yuan J, Jung YK. FcγRIIb mediates amyloid-β neurotoxicity and memory impairment in Alzheimer's disease. J Clin Invest. 2013 Jul 1;123(7):2791-802. doi: 10.1172/JCI66827. Epub 2013 Jun 10.
158. Tammaro A, Stroo I, Rampanelli E, Blank F, Butter LM, Claessen N, Takai T, Colonna M, Leemans JC, Florquin S, Dessing MC. Role of TREM1-DAP12 in renal inflammation during obstructive nephropathy. PLoS One. 2013 Dec 16;8(12):e82498. doi: 10.1371/journal.pone.0082498.
157. Montalvo V, Quigley L, Vistica BP, Boelte KC, Nugent LF, Takai T, McVicar DW, Gery I. Environmental factors determine DAP12 deficiency to either enhance or suppress immunopathogenic processes. Immunology 2013; 140(4):475-82. doi: 10.1111/imm.12158.
156. Matsumoto M, Sasaki Y, Yasuda K, Takai T, Muramatsu M, Yoshimoto T, Nakanishi K. IgG and IgE Collaboratively Accelerate Expulsion of Strongyloides venezuelensis in a Primary Infection. Infect. Immun., 81: 2518-27 (2013) doi: 10.1128/IAI.00285-13.
155. Kawano S, Lin Q, Amano H, Kaneko T, Nishikawa K, Tsurui H, Tada N, Nishimura H, Takai T, Shirai T, Takasaki Y, Hirose S. Phenotype conversion from rheumatoid arthritis to systemic lupus erythematosus by introduction of Yaa mutation into FcγRIIB-deficient C57BL/6 mice. Eur J Immunol. 2013 Mar;43(3):770-8. doi: 10.1002/eji.201243057. Epub 2013 Jan 25.
154. Tanaka J, Hirano K, Sakamoto Y, Sugahara-Tobinai A, Endo S, Ito-Matsuoka Y, Nakano A, Inui M, Nitschke L, Takai T. Intravenous immunoglobulin suppresses IL-10 production by activated B cells in vitro. Open J. Immunol. 2(4): 149-160, 2012 (DOI: 10.4236/oji.2012.24019)
153. Kuroki K, Hiorse K, Okabe Y, Fukunaga Y, Takahashi A, Shiroishi M, Kajikawa M, Tabata S, Nakamura S, Takai T, Koyanagi S, Ohdo S, Maenaka K. The long-term immunosuppressive effects of disulfide-linked HLA-G dimer in mice with collagen-induced arthritis. Human Immunol. Dec. 29, 2012 (doi:pii: S0198-8859(12)00688-X. 10.1016/j.humimm.2012.11.060)
152. Nakayama M, Kurokawa K, Nakamura K, Lee BL, Sekimizu K, Kubagawa H, Hiramatsu K, Yagita H, Okumura K, Takai T, Uderhill DM, Aderem A, Ogasawara K. Inhibitory receptor PIR-B is exploited by Staphylococcus aureus for virulence. J. Immunol.189: 5903-11, 2012. (doi: 10.4049/jimmunol.1201940)
151. Mitsuhashi Y, Nakamura A, Endo S, Takeda K, Yabe-Wada T, Nukiwa T, Takai T. Regulation of plasmacytoid dendritic cell responses by PIR-B. Blood 120: 3256-9. 2012. doi:10.1182/blood-2012-03-419093
150. Zangi L, Klionsky YZ, Yarimi L, Bacher-Lustig E, Edelshtein Y, Shezen E, Hagin D, Ito Y, Takai T, Reichi-Zeliger S, Lask A, Milstein O, Jung S, Shinder V, Reisner Y. Deletion of cognate CD8 T-cells by immature dendritic cells: a novel role for perforin, Granzyme A, TREM-1 and TLR7. Blood 120(8):1647-57, 2012 (doi: 10.1182/blood-2012-02-410803)
149. Wong WF, Kohu K, Nakamura A, Ebina M, Kikuchi T, Tazawa R, Tanaka K, Kon S, Funaki T, Sugahara-Tobinai A, Looi CY, Endo S, Funayama R, Kurokawa M, Habu S, Ishii N, Fkumoto M, Nakata K, Takai T, Satake M. Runx1 deficiency in CD4+ T cells causes fatal autoimmune inflammatory lung disease due to spontaneous hyperactivation of cells. J. Immunol. 2012; 188: 5408-5420; Epub 2 May 2012; doi: 10.4049/jimmunol.1102991
148. Kikuchi T, Kasuya R, Endo S, Nakamura A, Takai T, Metzler-Nolte N, Tohji K, and Balachandran J. Preparation of magnetite aqueous dispersion for magnetic fluid hyperthermia. J. Magn. Magn. Mater. 323: 1216-1222 (2011)
147. Nakayama M, Takeda K, Kawano M, Takai T, Ishii N, Ogasawara K. Natural killer (NK)-dendritic cell interactions generate MHC class II-dressed NK cells that regulate CD4+ T cells. Proc. Natl. Acad. Sci. USA. 108: 18360-18365 (2011).
146. Sato-Hayashizaki A, Ohtsuji M, Lin Q, Hou R, Ohtsuji N, Nishikawa K, Tsurui H, Sudo K, Ono M, Izui S, Shirai T, Takai T, Nishimura H, Hirose S.Presumptive role of 129 strain-derived Sle16 locus in rheumatoid arthritis in a new mouse model with Fcγ receptor type IIb-deficient C57BL/6 genetic background. Arthritis Rheum. 63: 2930-2938 (2011).
145. McCormick S, Shaler CR, Small CL, Horvath C, Damjanovic D, Brown EG, Aoki N, Takai T, Xing Z. Control of pathogenic CD4 T cells and lethal immunopathology by signaling immunoadaptor DAP12 during influenza infection. J Immunol. 187: 4280-4292 (2011).
144. Fujita Y, Takashima R, Endo S, Takai T, Yamashita T. The p75 receptor mediates axon growth inhibition through an association with PIR-B. Cell Death Dis. 2: e198 (2011).
143. 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. The immunoreceptor adapter protein DAP12 suppresses B lymphocyte–driven adaptive immune responses. J Exp Med. 208:1661-1671 (2011).
142. Matsushita H, Endo S, Kobayashi E, Kobayashi K, Kitaguchi K, Kuroki K,
Soderhall A, Maenaka K, Nakamura A, Takai T. Differential but competitive binding of Nogo and MHCI to PIR-B provides an inhibition of cells. J. Biol. Chem. 286: 25739-25747 (2011).
141. Arita K, Endo S, Kaifu T, Kitaguchi K, Nakamura A, Ohmori H, Kohu K, Satake M, Takai T. Transcriptional activation of the Pirb gene in B cells by PU.1 and Runx3. J. Immunol. 186: 7050-7059 (2011).
140. Ma G, Pan PY, Eisenstein S, Divino CM, Lowell C, Takai T, Chen SH. Paired immunoglobulin like receptor-B regulates the suppressive function and fate of myeloid derived suppressor cells. Immunity 34: 385-395 (2011).
139. Fujita Y, Endo S, Takai T, Yamashita T. Myelin suppresses axon regeneration by PIR-B/SHP-mediated inhibition of Trk activity. EMBO J. 30: 1389-1401 (2011).
138. 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. Mycobacterial hypersensitivity pneumonitis requires TLR9-MyD88 in lung CD11b+ CD11c+ cells. Eur. Respir J. 38: 688-701 (2011).
137. Nakamura, Y., Fujita, Y., Ueno, M., Takai, T. and Yamashita, T. Paired immunoglobulin-like receptor B knockout does not enhance axonal regeneration or locomotor recovery after spinal cord injury. J. Biol. Chem. 286: 1876-1883 (2010).
136. Takai T, Nakamura A, Endo S. Role of PIR-B in Autoimmune Glomerulonephritis. J. Biomed. Biotech. 2011: 275302 (2011).
136. Omoto S, Ueno M, Mochio S, Takai T, Yamashita T. Genetic deletion of paired immunoglobulin-like receptor B does not promote axonal plasticity or functional recovery after traumatic brain injury. J. Neurosci. 30: 13045-13052 (2010).
135. Yamamoto M, Kobayashi K, Ishikawa Y, Nakata K, Funada Y, Kotani Y, Masuda A, Takai T, Azuma T, Yoshida M, Nishimura Y. 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. Clin. Exp. Immunol. 162: 315-324 (2010).
134. Enomoto Y, Yamanishi Y, Izawa K, Kaitani A, Takahashi M, Maehara A, Oki T, Takamatsu R, Kajikawa M, Takai T, Kitamura T, Kitaura J. Characterization of leukocyte mono-immunoglobulin-like receptor 7 (LMIR7)/CLM-3 as an activating receptor: its similarities to and differences from LMIR4/CLM-5. J. Biol. Chem. 285: 35274-35283 (2010).
133. 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. TIM1 is an endogenous ligand for LMIR5/CD300b: LMIR5 deficiency ameliorates mouse kidney ischemia/reperfusion injury. J. Exp. Med. 207: 1501-1511 (2010).
132. Takai T, Karasuyama H. The study of allergy by Japanese researchers: a historical perspective. Int. Immunol. 12: 1311-1316 (2009).
131. Kubo T, Uchida Y, Watanabe Y, Abe M, Nakamura A, Ono M, Akira S, Takai T. Augmented TLR9-induced Btk activation in PIR-B-deficient B-1 cells provokes excessive autoantibody production and autoimmunity. J. Exp. Med. 206: 1971–1982 (2009).
130. Imada M, Masuda M, Satoh R, Ito Y, Goto Y, Matsuoka T, Endo S, Nakamura A, Kawamoto H, Takai T: Ectopically expressed PIR-B on T cells constitutively binds to MHC class I and attenuates T helper type 1 responses. Int. Immunol. 21:1151-1161 (2009).
129. Otero K, Turnbull IR, Poliani L, Vermi W, Aoshi T, Takai T, Stanley SL, Miller M, Colonna M. MCSF induces macrophage proliferatin and survival through a DAP12-β-catenin signaling pathway. Nat. Immunol. 10: 734–743 (2009).
128. Tassi I, Le Friec G, Gilfillan S, Takai T, Yokoyama WM, Colonna M. DAP10 associates with Ly49 receptors but contributes minimally to their expression and function in vivo. Eur. J. Immunol. 39:1129–1135 (2009).
127. Orr MT, Sun JC, Arase H, Phillips JH, Takai T, Lanier LL. DAP12-independent Ly49H-mediated NK cell responses against mouse cytomegalovirus. J. Exp. Med. 206: 807–817 (2009)
126. Li L, Kaifu T, Obinata M, Takai T: Peroxiredoxin III-deficiency Sensitizes Macrophages to Oxidative Stress. J. Biochem. 145: 425–427 (2009).
125. Inui M, Kikuchi Y, Aoki N, Endo S, Maeda T, Sugahara-Tobinai A, Nakamura A, Kumanogoh A, Colonna M, Takai T. Signal adaptor DAP10 associates with MDL-1 and triggers osteoclastogenesis in cooperation with DAP12. Proc. Nat.l Acad. Sci. USA. 106: 4816−4821 (2009).
124. Helming L, Tomasello E, Kyriakides TR, Martinez FO, Takai T, Gordon S, Vivier E. Essential role of DAP12 signaling in macrophage programming into a fusion-competent state. Sci. Signal. 1: ra11 (2008).
123. Hida S, Yamasaki S, Sakamoto Y, Takamoto M, Obata K, Takai T, Karasuyama H, Sugane K, Saito T, Taki S. Fc receptor γ -chain, a constitutive component of the interleukin-3 receptor, is required for interleukin 3-induced interleukin 4 production in basophils. Nat. Immunol. 10: 214–222 (2009).
122. Endo S, Sakamoto Y, Nakamura A, Takai T. Regulation of cytotoxic T lymphocyte triggering by PIR-B on dendritic cells. Proc. Natl. Acad. Sci. USA. 105: 14515−14520 (2008).
121. Mori Y, Tsuji S, Inui M, Sakamoto Y, Endo S, Ito Y, Fujimura S, Koga T, Nakamura A, Takayanagi H, Itoi E, Takai T. Inhibitory immunoglobulin-like receptors LILRB and PIR-B negatively regulate osteoclast development. J. Immunol. 181: 4742−4751 (2008).
120. Torii I, Oka S, Hotomi M, Benjamin WH Jr, Takai T, Kearney JF, Briles DE, Kubagawa H. PIR-B-deficient mice are susceptible to Salmonella infection. J. Immunol. 181: 4229−4239 (2008).
119. Kasai S, Inui M, Nakamura K, Kakizaki Y, Endo S, Nakamura A, Ito S, Takai T. A novel regulatory role of gp49B on dendritic cells in T cell priming. Eur. J. Immunol. 38: 2426−2437 (2008).
118. Kofu 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. Comparison of 30 immunity-related genes from thecommon marmoset with orthologues from human and mouse. Tohoku J. Exp. Med. 215: 167−180 (2008).
117. 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. Fcγ Receptor Regulation of Citrobacter rodentium Infection. Infect. Immunity 76: 1728−1737 (2008).
116. 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. Tyrosine kinases Btk and Tec regulate osteoclast differentiation by linking RANK and ITAM signals. Cell 132: 794-806 (2008).
115. 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. Analysis of mouse LMIR5/CLM7 as an activating receptor: differential regulation of LMIR5/CLM7 in ouse versus human cells. Blood 111: 688−698 (2008).
114. Giurisato E, Cella M, Takai T, Kurosaki T, Feng Y, Longmore GD, Colonna M, Shaw AS. PI3-kinase activation is required to form the NKG2D immunological synapse. Mol. Cell. Biol. 27: 8583−8599 (2007).
113. Kojima T, Obata K, Muikai K, Sato S, Takai T, Minegishi Y, Karasuyama H. A CD200 receptor-like protein CD200R3 functions as an activating receptor expressed exclusively on basophils and mast cells. J. Immunol. 179: 7093−7100 (2007).
112. Divangahi M, Yang T, Kugathasan K, McCormick S, Takenaka S, Gaschler G, Ashkar A, StampfliM, Gauldie J, Bramson J, Takai T, Brown E, Yokoyama WM, Aoki N and Xing Z.Critical Negative Regulation of type 1 T cell immunity and immunopathology by signaling adaptor DAP12 during intracellular infection. J. Immunol. 179: 4015−4026 (2007).
111. Inoue Y, Kaifu T, Sugahara−Tobinai A, Nakamura A, Miyazaki J-I, Takai T. Activating Fcγ receptors participate in the development of autoimmune diabetes in NOD mice. J. Immunol. 179: 764−774 (2007).
110. Ochi S, Shinohara M, Sato K, Gober H-J, Koga T, Kodama T, Takai T, Miyasaka N, Takayanagi H. Pathological role of osteoclast costimulation in arthritis-induced bone loss. Proc. Natl. Acad. Sci. USA 104: 11394−11399 (2007).
109. Hara H, Ishihara C, Takeuchi A, Xue L, Morris SW, Imanishi T, Inui M, Takai T, Shibuya A, Koseki H, Yoshida H, Penninger JM, Saito T. The adaptor protein CARD9 is essential for the activation of myeloid cells through ITAM-associated and Toll-like receptors. Nat. Immunol. 8: 619−629 (2007).
108. Masuda A*, Nakamura A* (*equal contributor), Maeda T, Sakamoto Y, Takai, T. Cis binding between inhibitory receptors and MHC class I can regulate mast cell activation. J. Exp. Med. 204: 907−920 (2007).
107. Izawa K, Kitaura J, Yamanishi Y, Matsuoka T, Oki T, Shibata F, Kumagai H, Nakajima H, Maeda-Yamamoto M, Hauchins JP, Tybulewicz VL, Takai T, Kitamura T. Functional analysis of an activating receptor LMIR4 as a counterpart of an inhibitory receptor LMIR3. J. Biol. Chem. 282: 17997−18008 (2007).
106. Li L, Shoji W, Takano H, Nishimura N, Aoki Y, Takahashi R, Goto S, Kaifu T, Takai T, Obinata M. Increased susceptibility of MER5 (peroxiredoxin III) knockout mice to LPS-induced oxidative stress. Biochem. Biophys. Res. Commun. 355: 715−721 (2007).
105. Nakayama M, Underhill DM, Petersen TW, Li B, Kitamura T, Takai T, Aderem A. Paired Ig-like receptors bind to bacteria and shape TLR-mediated cytokine production. J. Immunol. 178: 4250−4259 (2007).
104. Nakahashi C, Tahara-Hanaoka S, Totsuka N, Okoshi Y, Takai T, Ohkochi N, Honda S-i, Shibuya K, Shibuya A. Dual assemblies of an activating immune receptor, MAIR-II, with ITAM-bearing adaptors DAP12 and FcRγ chain on peritoneal macrophages. J. Immunol. 178: 765−770 (2007).
103. Sato K, Suematsu A, Nakashima T, Takemoto-Kimura S, Aoki K, Morishita Y, Asahara H, Ohya K, Yamaguchi A, Takai T, Kodama T, Chatila TA, Bito H, Takayanagi H. Regulation of osteoclast differentiation and function by the CaMK/CREB pathway. Nat. Med. 12:1410−1416 (2007).
102. Kitamura K*, Takeda K*, Koya T*, Miyahara N* (*equal contributors), Kodama T, Dakhama A, Takai T, Hirano A, Tanimoto M, Harada M, Gelfand EW. Critical role of the Fc receptor γ-chain on APCs in the development of allergen-induced airway hyperresponsiveness and inflammation. J. Immunol. 178: 480−488 (2007).
101. Iizuka S, Kaifu T, Nakamura A, Obinata M, Takai T. Establishment and functional characterization of novel natural killer cell lines derived from a temperature-sensitive SV40 large T antigen transgenic mouse. J. Biochem. (Tokyo) 140: 255−265 (2006).
100. Kanehira M, Kaifu T, Maya K, Kaji M, Nakamura A, Obinata M, Takai T. Novel mast cell lines with enhanced proliferative and degranulative abilities established from temperature-sensitive SV40 large T antigen transgenic mice. J. Biochem. (Tokyo) 140: 211−220 (2006).
99. Takegahara N, Takamatsu H, Toyofuku T, Tsujimura T, Okuno T, Yukawa K, Mizui M, Yamamoto M, Prasad DV, Suzuki K, Ishii M, Terai K, Moriya M, Nakatsuji Y, Sakoda S, Sato S, Akira S, Takeda K, Inui M, Takai T, Ikawa M, Okabe M, Kumanogoh A, Kikutani H. Plexin-A1 and its interaction with DAP12 in immune responses and bone homeostasis. Nat. Cell Biol. 8: 615−622 (2006).
98. Graham DB, Cella M, Giurisato E, Fujikawa K, Miletic AV, Kloeppel T, Brim K, Takai T, Shaw AS, Colonna M, Swat W. Vav1 controls DAP10-mediated natural cytotoxicity by regulating actin and microtubule dynamics. J. Immunol. 177: 2349−2355 (2006).
97. Blasius AL, Cella M, Maldonado J, Takai T, Colonna M. Siglec-H is an IPC-specific receptor that modulates type I IFN secretion through DAP12. Blood 107: 2474−2476 (2006).
96. Okazaki T, Otaka Y, Wang J, Hiai H, Takai T, Ravetch JV, Honjo T. Hydronephrosis associated with anti-urothelial and anti-nuclear autoantibodies in BALB/c-Fcgr2b-/-Pdcd1-/-mice. J. Exp. Med. 202: 1643−1648 (2005).
95. Turnbull IR, McDunn JE, Takai T, Townsend RR, Cobb JP, Colonna M. DAP12 (KARAP) amplifies inflammation and increases mortality from endotoxemia and septic peritonitis. J. Exp. Med. 202: 363−369 (2005).
94. Xie X, He H, Colonna M, Seya T, Takai T, Croy BA. Pathways participating in activation of mouse uterine natural killer cells during pregnancy. Biol. Reprod. 73: 510−518 (2005).
93. Zhang H, Meng F, Chu C-L, Takai T, Lowell C. The src-family kinases Hck and Fgr negatively regulate neutrophil and dendritic cell chemokine signaling via PIR-B. Immunity 22: 235−246 (2005).
92. Ebihara, S., Endo, S., Ito, K., Ito, Y., Akiyama, K., Obinata, M., Takai, T. Immortalized dendritic cell line with efficient antigen-presenting ability established from transgenic mice harboring temperature-sensitive SV40 large T-antigen gene. J. Biochem. (Tokyo) 136: 321−328 (2004).
91. Pereira S, Zhang H, Takai T, Lowell CA. The inhibitory receptor PIR-B negatively regulates neutrophil and macrophage integrin signaling. J. Immunol. 173: 5757−5765 (2004).
90. Nakamura A, Kobayashi E, Takai T. Exacerbated graft-versus-host disease in Pirb-/- mice. Nat. Immunol. 5: 623−629 (2004).
89. Koga T*, Inui M*, Inoue K, Kim S, Suematsu A, Kobayashi E, Iwata T, Ohnishi H, Matozaki T, Kodama T, Taniguchi T, Takayanagi H, Takai T. (*equal contributor) Costimulatory signals mediated by the ITAM motif cooperate with RANKL for bone homeostasis. Nature 428, 758–763 (2004).
88. Yamaguchi, A., Katsuyama, K., Nagahama, K., Takai, T., Aoki, I., Yamanaka, S. Possible role of autoantibody in the pathophysiology of GM2 angliosidoses. J. Clin. Invest. 113: 200–208 (2004).
87. Takai, T. Role of paired immunoglobulin-like receptor (PIR)-B in humoral immune response. Allergol. Int. 2: 93–99 (2004).
86. Nakamura, A., Takai , T. A role of FcγRIIB in the development of collagen-induced arthritis. Review. Biomed. Pharmacother. 5: 623–629 (2004).
85. Watanabe, T., Okano, M., Hattori, H., Yoshino, T., Ohno, N., Ohta, N., Sugata, Y., Orita, Y., Takai, T., Nishizaki, K. Roles of FcγRIIB in nasal eosinophilia and IgE production in murine allergic rhinitis. Am. J. Respir. Crit. Care Med. 169: 105–112 (2004).
84. Yada, A., Ebihara, S., Matsumura, K., Akiyama, K., Aiba, S., and Takai, T. Contribution of Fcγ receptors to antigen presentation and elicitation of humoral response in vivo. Cell. Immunol. 225: 21–32 (2003).
83. Nakahara, J., Tan-Takeuchi, K., Seiwa, C, Gotoh, M., Kaifu, T., Ujike, A., Inui, M., Yagi, T., Aiso, S., Takai, T., and Asou, H. Signaling via immunoglobulin Fc receptors induces oligodendrocyte precursor cell differentiation. Dev. Cell 4: 841–852 (2003).
82. Takai, T., Nakamura, A., Akiyama, K. Fc receptors as potential targets for treatment of allergy, autoimmune disease and cancer. Curr. Drug Targets Immune Endocr. Metabol. Disorders. 3: 187–197 (2003).
81. Nakamura, A., Nukiwa, T., Takai, T. Deregulation of peripheral B cell development in enhanced severity of collagen-induced arthritis in Fc γRIIB-deficient mice. J. Autoimmu. 20: 227–236 (2003).
80. Nakamura, A., Mori, Y., Hagiwara, K., Suzuki, T., Sakakibara, T., Kikuchi, T., Igarashi, T., Ebina, M., Miyazaki, J., Takai, T., Nukiwa, T. Increased susceptibility to LPS-induced endotoxin shock in secretory leukoprotease inhibitor (SLPI)-deficient mice. J. Exp. Med. 197: 669–674 (2003).
79. Yajima K, Nakamura A, Sugahara A, Takai T. FcγRIIB deficiency with Fas mutation is sufficient for the development of systemic autoimmune disease. Eur. J. Immunol. 33: 1020–1029 (2003).
78. Taube C, Takeda K, Dakhama A, Rha Y, Joetham A, Park J.-W, Ballhorn A, Takai T, Benchich KR, Nick JA, Gelfand EW. Transient neutrophil inflammation after allergen challenge is dependent on specific antibodies and Fc receptors. J. Immunol. 170: 4301–4309 (2003).
77. Nieswandt, B., Bergmeier, W., Schulte, V., Takai, T., Baumann, U., Schmidt, R.E., Zirngibl, H., Bloch, W. and Gessner, J.E. Targeting of platelet integrin αIIbβ3 determines systemic reaction and bleeding in murine thrombocytopenia regulated by activating and inhibitory FcγRs. Int. Immunol. 15: 341–349 (2003).
76. Akiyama K, Ebihara S, Yada, A., Matsumura, K., Aiba, S., Nukiwa, T., and Takai T. Targeting of apoptotic tumor cells to Fcγ receptors provides efficient and versatile vaccination against tumors by dendritic cells. J. Immunol. 170: 1641–1648 (2003).
75. Kaifu, T., Nakahara, J., Inui, M., Mishima, K., Momiyama, T., Kaji, M., Sugahara, A., Koito, H., Ujike-Asai, A., Nakamura, A., Kanazawa, K., Tan-Takeuchi, K., Iwasaki, K., Yokoyama, W.M., Kudo, A., Fujiwara, M., Asou, H., and Takai, T. Osteopetrosis and thalamic hypomyelinosis with synaptic degeneration in DAP12-deficient mice. J. Clin. Invest. 111: 323–332 (2003).
74. Takai T. Roles of Fc receptors in autoimmunity. Nat. Rev. Immunol. 2: 580–592 (2002).
73. Ujike A, Takeda K, Nakamura A, Ebihara S, Akiyama K, Takai T. Impaired dendritic cell maturation and increased TH2 responses in PIR-B-/- mice. Nat. Immunol. 3: 542–548 (2002).
72. Makabe-Kobayashi Y, Hori Y, Adachi T, Ishigaki-Suzuki S, Kikuchi Y, Kagaya Y, Shirato K, Nagy A, Ujike A, Takai T, Watanabe T, and Ohtsu H. The control effect of histamine on the body temperature and respiratory function in IgE-dependent systemic anaphylaxis. J. Allergy Clin. Immunol. 110, 298–303 (2002).
71. Kato I, Takai T, and Kudo A. The pre-B cell receptor signaling for apoptosis is negatively regulated by FcγRIIB. J. Immunol 168: 629-634 (2002).
70. Kubo, S., Matsuoka, K., Taya, C., Kitamura, F., Takai, T., Yonekawa, H., Karasuyama, H. Drastic up-regulation of FcεRI on mast cells is induced by IgE binding through stabilization and accumulation of FcμRI on the cell surface. J. Immunol. 167: 3427–3434 (2001).
69. Takai, T., and Ono, M. Activating and inhibitory nature of the murine paired Ig-like receptor (PIR) family. Immun. Rev. 181: 215–222 (2001).
68. Yuasa, T., Ono, M., Watanabe, T., and Takai, T. Lyn is essential for Fcγ receptor III-mediated systemic anaphylaxis but not for the Arthus reaction. J. Exp. Med. 193: 563–572 (2001).
67. Kaji, K., Takeshita, S., Miyake, K., Takai, T., and Kudo, A. Functional association of CD9 molecule with FcγIII receptor in macrophages. J. Immunol. 166: 3256–3265 (2001).
66. Yoneto, T., Waki, S., Takai, T., Tagawa, Y., Iwakura, Y., Mizuguchi, J., Nariuchi, H., and Yoshimoto, T. A critical role of Fc receptor-mediated antibody-dependent phagocytosis in the host resistance to blood- stage plasmodium berghei XAT infection. J. Immunol. 166: 6236–6241 (2001).
65. Lee, K.H., Ono, M., Inui, M., Yuasa, T., and Takai, T. Stimulatory function of gp49A, a murine Ig-like receptor, in RBL-2H3 cells. J. Immunol. 165: 4970–4977 (2000).
64. Onah DN, Uchiyama F, Nagakui Y, Ono M, Takai T, Nawa Y. Mucosal defence against gastrointestinal nematodes: Responses of mucosal mast cells and mouse mast cell protease 1 during primary Strongyloides venezuelensis infection in FcRγ-knockout mice. Infect. Immun. 68: 4968–4971 (2000).
63. Wakayama, H., Hasegawa, Y., Kawabe, T., Hara, T., Matsuo, S., Mizuno, M., Takai,T., Kikutani, H., Shimokata, K. Abolition of anti-glomerular basement membrane antibody-mediated glomerulonephritis in FcRγ-deficient mice. Eur. J. Immunol. 30: 1182–1190 (2000).
62. Schiller, C., Janssen-Graalfs, I., Baumann, U., Schwerter-Strumpf, K., Izui, S., Takai, T., Schmidt, R.E., and Gessner, J.E. Mouse FcgRII is a negative regulator of FcγRIII in IgG immune complex triggered inflammation but not in autoantibody induced hemolysis. Eur. J. Immunol. 30:481–490 (2000).
61. Nakamura, A., Yuasa, T., Ujike, A., Ono, M., Nukiwa, T., Ravetch, J.V., Takai, T. Fcγ receptor IIB-deficient mice develop Goodpasture's syndrome upon immunization with type IV collagen: A novel murine model for autoimmune glomerular basement membrane disease. J. Exp. Med. 191: 899–906 (2000).
60. Cortegano, I., del Pozo, V., C?daba, B., Arrieta, I., Gallardo, S., Rojo, M., Aceituno, E., Takai, T., Verbeek, S., Palomino, P., Liu, F.-T., and Lahoz, C. Interaction between galectin-3 and FcγRII induces down-regulation of IL-5 gene: Implication of the promoter sequence IL-5REIII. Glycobiol. 10: 237–242 (2000).

1999 total 59 reports.

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