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Kiyoshi Takatsu, Ph.D.
Professor
Division of Immunology,
Department of Microbiology and Immunology,
Institute of Medical Science,
University of Tokyo, Tokyo 108-8639, Japan |
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Education:
| 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 |
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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. |
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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 V11+ 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 V11+ 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 C1 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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