6th The Awaji International Forum on Infection and Immunity  
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Kiyoshi Takatsu, Ph.D.

Division of Immunology,
Department of Microbiology and Immunology,
Institute of Medical Science,
University of Tokyo, Tokyo 108-8639, Japan

1963 - 1967 Bachelor of Pharmaceutical Science, Toyama University
1967 - 1969 Master of Pharmaceutical Science, Toyama University
1969 - 1973 Doctor of Medical Science, Osaka University Medical School

Professional Experience:

1973 - 1976 Postdoctoral fellow, Johns Hopkins University, School of Medicine
1976 - 1978 Assistant Professor, Osaka University Medical School.
1978 - 1982 Associate Professor, Osaka University Medical School.
1982 - 1992 Professor, School of Medicine, Kumamoto University.
1990 - 2000 Professor, Institute of Medical Science, University of Tokyo.
2000 - present Professor, Division of Immunology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo.
Selected publications:

Takatsu K, Ishizaka T, and Ishizaka K. Biological significance of disulfide bonds in human IgE molecule. J. Immunol. 1975. 114: 1838-1846.

Takatsu K, and Ishizaka K. Reaginic antibody formation in the mouse. VIII. Depression of the on-going IgE antibody formation by suppressor T cells. J. Immunol. 1976, 116: 1257-1266.

Takatsu K, and Ishizaka K. Reaginic antibody formation in the mouse. IX. Enhancement of suppressor and helper cell activities of primed spleen cells. J. Immunol. 1977, 118: 151-158.

Takatsu K, Tominaga A, and HamaokaT. Antigen-induced T cell-replacing factor (TRF). I. Functional characterization of a TRF Producing Helper T Cell Subset and Genetic Studies on TRF Production. J. Immunol. 1980, 123: 2414-2422.

Takatsu K, Tanaka K, Tominaga, A., Kumahara, Y., and Hamaoka, T. Antigen-induced T cell-replacing factor (TRF). III. Establishment of T cell hybrid clone continuously producing TRF and functional analysis of released TRF. J. Immunol. 1980, 125: 2646-2653.

Takatsu K, Sano Y, Tomita S, Hashimoto N, and Hamaoka T. Antibody against T cell-replacing factor acceptor site(s) augments in vivo primary IgM responses to suboptimal doses of heterologous erythrocytes. Nature 1981, 292:360-362.

Howard M, Farrar J, Hilfiker M, Johnson B, Takatsu K, Hamaoka T, and Paul WE. Identification of a T cell growth factor distinct from interleukin 2. J. Exp. Med. 1982, 155: 914-923.

Takatsu K, Harada N, Hara Y, Takahama Y, Yamada G, Dobashi K, and Hamaoka T. Purification and physicochemical characterization of murine T cell-replacing factor (TRF). J. Immunol. 1985, 134:382-389.

Harada N, Kikuchi Y, Tominaga A, Takaki S, and Takatsu K. BCGFII Activity on activated B cells of a purified murine T cell-replacing factor (TRF) from a T cell hybridoma (B151K12). J. Immunol. 1985, 134: 3944-3951.

Kinashi T, Harada N, Severinson E, Tanabe T, Takatsu K, et al. Cloning of complementary DNA for T-Cell Replacing Factor and Identity with B-Cell Growth Factor II. Nature 1986, 324:70-73.

Takatsu K, Kikuchi Y, Matsumoto M, Harada N., et al. Interleukin 5, a T-cell-derived B-cell differentiation factor also induces cytotoxic T lymphocytes. Proc. Natl. Acad. Sci. USA 1987, 84: 4234-4238.

Loughnan MS, Takatsu K, Harada N, and Nossal GJV. T-cell-replacing factor (interleukin 5) induces expression of interleukin 2 receptors on murine splenic B cells. Proc. Natl. Acad. Sci. USA 1987, 84: 5399-5403.

Harada N, Takahashi T, Matsumoto M, Kinashi T and Takatsu K. Production of a monoclonal antibody useful in the molecular characterization of murine T-cell-replacing factor/B-cell growth factor II. Proc. Natl. Acad. Sci. USA. 1987, 84:4581-4585.

Matsumoto M, Tominaga A, Harada N, and Takatsu K. Role of T cell-replacing factor (TRF) in the murine B cell differentiation: Induction of increased levels of expression of secreted type IgM mRNA. J. Immunol. 1987, 38:1826-1833.

Yamaguchi Y, Suda T, Suda J, Eguchi M, Miura Y, Harad N, Tominaga A, and Takatsu K. Purified interleukin-5 supports the terminal differentiation and proliferation of murine eosinophilic precursors. J. Exp. Med. 1988; 167:43-56.

Yamaguchi Y, Hayashi Y, Sugama Y, Miura Y, Kasahara T, Kitamura S, Torisu M, Mita S, Tominaga A, Takatsu K, and Suda T. Highly purified murine interleukin (IL-5) stimulates eosinophil function and prolongs in vitro survival. IL-5 as an eosinophil chemotactic factor. J. Exp. Med. 1988, 167:1737-1742.

Mita S, Harada N, Naomi S, Hitoshi Y, Sakamoto K, Akagi K, Tominaga A, and Takatsu K. Receptors for T cell-replacing factor/interleukin 5. Specificity, quantitation and its implication. J. Exp. Med. 1988, 168:863-878.

Tominaga A, Matsumoto M, Harada N, Takahashi T, Kikuchi Y, and Takatsu K. Molecular properties and regulation of mRNA expression for murine T cell-replacing factor/IL-5. J. Immunol. 1988, 140: 1175-1181.

Mita S, Tominaga A, Hitoshi Y, Honjo T, Sakamoto M, Akagi M, Kikuchi Y, Yamaguchi N, and Takatsu K. Characterization of high-affinity receptors for interleukin-5 on interleukin 5 dependent cell lines. Proc. Natl. Acad. Sci. USA 86:2311-2315, 1989

Sonoda E, Matsumoto R, Hitoshi Y, Mita S, Ishii T, Sugimoto M, Araki S, Tominaga A, Yamaguchi N, and Takatsu K. Transforming growth factor-b induces IgA production and acts additively with IL-5 for IgA production. J. Exp. Med. 170:1415-1420, 1989

Yamaguchi N, Hitoshi Y, Mita S, Hosoya Y, Murata Y, Kikuchi Y, Tominaga A, and Takatsu K. Characterization of the murine interleukin 5 receptor by using a monoclonal antibody. Int. Immunol. 2: 181-187.

Hitoshi Y, Yamaguchi N, Mita S, Takaki S, Tominaga A, and Takatsu K. Distribution of IL-5 receptor-positive B cells: Expression of IL-5-receptor on Ly-1 (CD5)+ B cells. J. Immunol. 1990, 53:4218-4325.

Takaki S, Tominaga A, Hitoshi Y, Mita S, Sonoda E, Yamaguchi N, and Takatsu K. Molecular cloning and expression of the murine interleukin 5 receptor. EMBO J. 1990, 9:4367-4374.

Takaki S, Mita S, KitamuraT, Yonehara S, Tominaga A, Yamaguchi N, Miyajima A, and Takatsu K. Identification of the second subunit of the murine interleukin 5 receptor: interleukin-3 receptor-like protein, AIC2B is a component of the high affinity interleukin-5 receptor. EMBO J. 1991, 10:2833-2838.

Tominaga A, Takaki S, Koyama N, Katoh S, Matsumoto R, Migita M, Hitoshi Y, Hosoya Y, Yamauchi S, Kanai Y, Miyazaki J, Usuku G, Yamamura K, and Takatsu K. Transgenic mice expressing a B cell growth and differentiation factor gene (interleukin 5) develop eosinophilia and autoantibody production. J. Exp. Med. 1991, 173:429-438.

Corrigan CJ, Haczku A, Gemou-Engesaeth V, Doi S, Kikuchi Y, Takatsu K, Durham SR, and Kay AB. CD4-T Lymphocyte Activation in Asthma is accompanied by Increased Serum concentrations of Interleukin-5: Effect of Glucocorticoid Therapy. Am. Rev. Resp. Dis. 1993, 147:540-547.

Murata Y, Takaki S, Migita M, Kikuchi Y, Tominaga A, and Takatsu K. Molecular Cloning and Expression of the Human Interleukin 5 receptor. J. Exp. Med. 1992, 175:341-351.

Nakajima H, Iwamoto I, Tomoe S, Matsumura R, Tomioka H, Takatsu K, and Yoshida S. CD4+ T-Lymphocytes and Interleukin-5 Mediate Antigen-Induced Eosinophil Infiltration into the Mouse Trachea. Amr. Rev. Respir. Dis. 1992, 146:374-377.

Hitoshi Y, Okada Y, Sonoda E, Tominaga A, Makino M, Suzuki K, Kinoshita J, Komura K, Mizuochi T, and Takatsu K. Delayed Progression of a Murine retrovirus-Induced acquired immunodeficiency syndrome in X-linked immunodeficient mice. J. Exp. Med. 1993, 177:621-626.

Takaki S, Murata Y, Kitamura T, Miyajima A, Tominaga A, and Takatsu K. Reconstitution of the functional receptors for murine and human interleukin 5. J. Exp. Med. 1993, 177:1523-1529.

Mita S, Takaki S, Tominaga A, and Takatsu K. Comparative Analysis of Kinetic Binding, Internalization, and Degradation of IL-5 Receptors of High- and Low-Affinity. J. Immunol. 1993, 151:6924-6932.

Motojima S, Akutsu I, Fukuda T, Makino S, and Takatsu K. Clinical significance of mearing levels of sputum and serum ECP and serum IL-5 in bronchial asthma. Allergy 1993, 48:98-106.

Takaki S, Kanazawa H, Shiiba M, and Takatsu K. Critical cytoplasmic domain of the IL-5R  chain and its function in IL-5-mediated growth signal transduction. Mol. Cell. Biol. 1994, 12:7404-7413.

Satoh S, Katagiri T, Takaki S, Kikuchi Y, Hitoshi Y, Yonehara S, Tsukada S, Kitamura D, Watanabe T, Witte ON, and Takatsu K. IL-5 receptor-mediated tyrosine phosphorylation of SH2/SH3-containing proteins and activation of Bruton's tyrosine and JAk2 kinases. J. Exp. Med. 1994, 180:2101-2111.

Kinashi T, Escobedo JA, Williams LT, Takatsu K, and Springer TA. Receptor tyrosine kinase stimulates cell-matrix adhesion by phosphatidylinositol 3-kinase and phospholipase C-γ1 pathways. Blood 1995, 86:2086-2090.

Koike M, Kikuchi Y, Tominaga A, Takaki S, Akagi K, Miyazaki J, Yamamura K, and Takatsu K. Defect of IL-5-receptor-mediated signaling in B cells of X-linked immuno-deficient (XID) mice. Int. Immunol. 1995, 7:21-30.

Kikuchi Y., Yasue T, Yamashita Y, Miyake K, Kimoto M, and Takatsu K. CD38 ligation induces Btk activation and enhanced expression of IL-5 receptor a chain. Proc. Natl. Acad. Sci. USA, 1995, 92:10879-10883.

Li T, Tsukada S, Satterthwaite A, Park H, Havlik MH, Takatsu K, and Witte ON. Oncogenic activation of Bruton's tyrosine kinase (BTK) by a point mutation in its pleckstrin homology (PH) domain. Immunity 1995, 2:451-460.

Kinashi T, Escobedo JA, Williams LT, Takatsu K, and Springer TA. Receptor tyrosine kinase stimulates cell-matrix adhesion by phosphatidylinositol 3-kinase and phospholipase C-γ1 pathways. Blood 1995, 86:2086-2090.

Yoshida T, Ikuta K, Sugaya H, Maki K, Takagi M, Kanazawa H, Sunaga S, Kinashi T, Yoshimura K, Miyazaki J, Takaki S, and Takatsu K. Defective B-1 cell development and impaired immunity against Angiostrongylus cantonensis in IL-5Ra deficient mice. Immunity 1996, 4:483-494.

Yasue, T., Nishizumi, H., Aizawa, S., Yamamoto, T., Miyak,e K., Mizoguchi, C., Uehara, S., Kikuchi, Y,, and Takatsu K. A critical role of Lyn and Fyn for B cell responses to CD38 ligation and interleukin 5. Proc. Natl. Acad. Sci. USA. 1997, 94: 10307-10312.

Yanagisawa S. Koike M. Kariyone A. Nagai S, and Takatsu K. Mapping of V11+ helper T cell epitopes on mycobacterial antigen in mouse primed with Mycobacterium tuberculosis. Int Immunol. 1997, 9:227-237.

Ogata N, Kouro T, Yamada A, Koike M, Hanai N, Ishikawa T, and Takatsu K. JAK2 and JAK1 constitutively associate with an interleukin-5 (IL-5) receptor alpha and betac subunit, respectively, and are activated upon IL-5 stimulation. Blood 1998, 91:2264-2271.

Baba M. Kikuchi Y. Mori S. Kimoto H. Inui S. Sakaguchi N. Inoue J. Yamamoto T. Takemori T. Howard M. Takatsu K. Mouse germinal center B cells with the xid mutation retain responsiveness to antimouse CD40 antibodies but diminish IL-5 responsiveness. Int Immunol. 1997, 9:1463-1473.

Hiroi T, Yanagida M, Iijima H, Iwatani T, Yoshida T, Takatsu K, and Kiyono H. Deficiency of IL-5 receptor alpha-chain selectively influences the development of the common mucosal immune system independent IgA-producing B-1 cell in mucosa-associated tissues. J Immunol. 1999, 162:821-828.

Kinashi T, Asaoka T, Sagara H, Setoguchi R, Hirosawa K, and Takatsu K. Regulated adhesion by modulating affinity and subcellular localization of integrin VLA-5 (a5b1) in mast cells. J. Immunol.1999, 162:2850-2857.

Mizoguchi C, Uehara S, Akira S, and Takatsu K. Interleukin-5 induces IgG1 isotype switch recombination in mouse CD38-activated sIgD-positive B lymphocytes. J. Immunol. 1999, 162:2812-2819.

Kariyone A, Higuchi K, Yamamoto S, Kametaka AN, Harada M, Takahashi A, Harada N, Ogasawara K, Takatsu K. Identification of amino acid residues of the T-cell epitope of Mycobacteiurm tuberculosis α antigen critical for V11+ Th1 cells. Infect. Immun. 1999, 67:4312-4319.

Katagiri K, Hattori M, Minato N, Irie S, Takatsu K, and Kinashi T. Rap1 is a potent activation signal for leukocyte function-associated antigen 1 distinct from protein kinase C and phosphatidylinositol-3-OH kinase. Mol. Cell. Biol. 2000, 20:1956-1969.

Kinashi T, Katagiri K, Watanabe S, Vanhaesebroeck B, Downward J, and Takatsu K. Distinct mechanisms of α5β1 integrin activation by Ha-Ras and R-Ras. J. Biol. Chem. 2000, 275:22590-22596.

Takaki S, Sauer K, Iritani KM, Chien S, Ebihara Y, Tsuji K, Takatsu K, and Perlmutter RM. Control of B cell production by the adaptor protein, Lnk, a negative regulator of tyrosine kinase. Immunity 2000, 13:599-609.

Kikuchi Y, Hirano M, Seto M, and Takatsu K. Identification and characterization of a molecule, BAM11, that associates with the PH-domain of mouse Btk. Int. Immunol. 2000, 12:1397-1408.

Horikawa K, Kaku H, Nakajima H, Davey HW, Henninghausen L, Iwamoto I, Yasue T, Kariyone A, and Takatsu K. Essential role of signal transducer and activator of transcription (Stat) 5 for interleukin-5-dependent IgH switch recombination in mouse B cells. J. Immunol. 2001, 167: 5018-5026.

Moon B-G, Yoshida T, Nakao K, Shiiba M, Katsuki M, Takaki S, and Takatsu K. Functional dissection of the cytoplasmic subregions of the IL-5 receptor a chain in growth and IgG1 switch recombination of B cells. Immunology, 2001, 289-300.

Kouro T, Nagata K, Takaki S, Nisitani S, Hirano M, Wahl MI, Witte ON, Karasuyama H, Takatsu K. Bruton’s tyrosine kinase (Btk) is required for CD75b-mediated differentiation signal of pro-B to pre-B transition. Int. Immunol. 2001, 13: 485-493.

Yamada A, Takaki S, Hayashi FB, Georgopoulos K, Perlmutter RM, and Takatsu K. Identification and characterization of a transcriptional regulator for the lck proximal promoter. J. Biol. Chem. 2001, 276:18082-9.

Takaki S, Morita H, Tezuka Y, and Takatsu K. Enhanced hematopoiesis by hematopoietic stem cells lacking intracellular adaptor protein, Lnk. J. Exp. Med. 2002, 195: 151-160.

Takaki S, Morita H, Tezuka Y, and Takatsu K. Enhanced hematopoiesis by hematopoietic projenitor cells lacking intracellular adaptor protein, Lnk. J. Exp. Med. 2002, 195: 151-60.

Kaku H, Horikawa K, Obata Y, Kato I, Okamoto H, Sakaguchi N, Gerondakis S, and Takatsu K. Nuclear Factor B is required for CD38-mediated Induction of the C1 germline transcripts in murine B lymphocyte. Int. Immunol. 2002, 14:1055-1064.

Takaki S, Tezuka Y, Sauer K, Kubo C, Kwon S-M, Armstead E, Nakao K, Katsuki M, Perlmutter RM, and Takatsu K. Impaired lymphopoiesis and altered B cell subpopulations in mice overexpressing Lnk adaptor protein. J. Immunol. 2003, 170: 703-710.
Nobuhisa I, Takizawa H, Takaki S, Inoue H, Okita K, Ueno M, Takatsu K, and Taga T. Regulation of hematopoetic development in the Aorta-gonad-mesonephros region mediated by Lnk adaptor protein. Mol. Cell. Biol. 2003, 23: 8486-8494.

Kariyone A, Kano H, Tamura T, Iwakura Y, and Takatsu K. Immunogenicity of Peptide-25 of Ag85B in Th1 development: role of IFN-γ. Int. Immunol. 2003, 15:1183-1194.

Suzuki H, Matsuda S, Terauchi Y, Fujiwara M, Ohteki T, Asano T, Behrens TW, Kouro T, Takatsu K, Kadowaki T, and Koyasu S. PI3K and Btk differentially regulate B cell antigen receptor-mediated signal transduction. Nat. Immunol. 2003, 4:280-286.

Kubo-Akashi C, IsekiI M, Kweon S-M, Takizawa H, Takatsu K, and Takaki S. Roles o conserved family of adaptor proteins, Lank, SH2-B and APS for mast cell development growth and functions: APS-deficiency causes impaired degranulation. Biochem. Biophys. Res. Commun. 2004, 315:356-362.

Iseki M., Kubo C, Kwon S-M, Yamaguchi A, Kataoka Y, Yoshida N, Takatsu K, and Takaki S. Negative regulatory role of APS, adaptor molecule containing PH and SH2 domains in B-1 cells and B cell receptor-mediated proliferation. Mol. Cell. Biol. 2004, 24:2243-2250.

Wen X, Zhang D, Abe M, Jiang Y, Matsuoka S, Nakamura K, Hamano Y, Kikuchi Y, Takatsu K, Shirai T, and Hirose S. Transgene-mediated over-expression of interleukin-5 suppresses autoimmune disease, but increases the risk of B cell chronic lymphocyte leukemia. Eur.J. Immunol. 2004, 34:2740-2749.

Moon B-G, Takaki S, Nishizumi H, Yamamoto T, and Takatsu K. Abrogation of autoimmune disease in Lyn-deficient mice by the deletion of IL-5 receptor chain gene Cell. Immunol. 2004, 228:110-118.

Tanaka H, Komai M, Nagao K, Ishizaki M, Kajiwara D, Takatsu K, Delespesse G, and Nagai H. Role of IL-5 and eosinophils in allergen-induced airway remodeling in mice. Am. J. Resp. Cell. Mol. Biol. 2004, 31: 62-68.

Moon B-Y, Takaki S, Miyake K, and Takatsu K. The role of IL-5 for mature B-1 cells in homeostatic proliferation, cell survival, and Ig production. J. Immunol. 2004, 172: 6020-6029.

Tamura T, Ariga H, Kinashi T, Uehara,S, Kikuchi T, Nakada M, Tokunaga T, Xu W, Kariyone A, Saito T, Kitamura T, Maxwell G, Takaki S. and Takatsu K. The role of antigenic peptide in CD4+ T helper phenotype development in a T cell receptor transgenic model. Int. Immunol. 2004, 15: 1691-1699.

Inoue H, Kato R, Fukuyama S, Nonami A, Taniguchi K, Matsumoto K, Nakano T, Tsuda M, Matsumura M, Kubo M, Ishikawa F, Takatsu K, Nakanishi Y, and Yoshimura A. Spred-1 negatively regulates allergen-induced airway eosinophilia and hyperresponsiveness. J. Exp Med. 2005, 201:73-82.

Iwasaki H, Mizuno S, Mayfield R, Shigematsu H, Arinobu Y, Gurish MF, Takatsu K, and Akashi K. Eosinophil lineage-committed progenitors are phenotypically isolatable in the murine bone marrow. J. Exp. Med. 2005, 201: 1891-1897.

Nagai Y, Kobayashi T, Motoi Y, Ishiguro K, Akashi S, Saitoh S, Kusumoto Y, Kaisho T, Akira S, Matsumoto M, Takatsu K and Miyake K. Radioprotectiv 105-MD-1 links toll-like receptors 2 (TLR2) and TLR4-MD2 with antibody production to microbial membrane. J Immunol. 2005, 174: 7043-7049.

Ema H, Sudo K, Seita J, Maeda A, Morita Y, Osawa M, Takatsu K, Takaki S, and Nakauchi H. Quantification of self-renewal capacity in single hematopoietic stem cellsfrom normal and Lnk-deficient mice. Dev. Cell 2005, 8:907-914.

Itakura A, Szczepanik M, Campos RA, Paliwal V, Majewska M, Matsuda H, Takatsu K, and Askenase PW. An hour after immunization peritoneal B-1 cells are activated to migrate to lymphoid organs where within 1 day they produce IgM antibodies that initiate elicitation of contact sensitivity. J. Immunol. 2005, 175:7170-7178.

Tsukamoto Y, Uehara S, Mizoguchi C, Sato A, Horikawa K, and Takatsu K. Requirement of 8-mercaptoguanosine as a costimulus for IL-4-dependent  to 1 class switch recombination in CD38-activated B cells. Biochem. Biophys. Res. Commun. 2005, 336: 625-633.

Takizawa H, Kubo-Akashi C, Nobuhisa I, Taga T, Kwon S.M., Iseki M,Taga, T., Takatsu K, Takaki S. Enhanced engraftment of hematopoietic stem/progenitor cells by the transient inhibition of an intracellular adaptor protein, Lnk. Blood. 2006, 107: 2968-75.

Kikuchi T, Uehara S, Ariga H, Tokunaga T, Kariyone A, Akira S, Tamura T, and Takatsu K. Augmented induction of CD8+ cytotoxic T cell response and antitumor resistance by Th1-inducing peptide. Immunology 2006, 117:47-58.

Horikawa K, and Takatsu K. IL-5 regulates the gene expression, involved in B cell terminal maturation Immunology, 2006, in press.

Nagai Y, Garrett KP, Ohta S, Uleng B, Kouro T, Akira S, Takatsu K, and Kincade P. Toll-like receptors on hematopoietic progenitor cells stimulate innate immune system replenishment. Immunity, 2006, in press.

Itakura A, Kikuchi Y, Kouro T, Ikutani M, Takaki S, and Takatsu K. Interleukin 5 plays an essential role in elicitation of contact sensitivity through dual effects on eosinophils and B-1 cells. Int. Archives Allergy Immunol. 2006, In press.

Wakabayashi Y, Kobayashi M, Akashi-Takamura S, Konno K, Takahashi K, Ishii T, Mizutani T, Iba H, Takaki S, Takatsu K, Oda Y, Saitoh S, and Miyake K. A protein associated with toll-like receptor 4 (PRAT4A) regulates cell surface expression of TLR4. J. Immunol. 2006, in press.
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