Tadamitsu Kishimoto

Suppressor of cytokine signaling-1 ameliorates dextran sulfate sodium-induced colitis in mice (2008)

Horino, Jiro, Fujimoto, Minoru, Terabe, Fumitaka, Serada, Satoshi, Takahashi, Tsuyoshi, Soma, Yoshihito, ...

Inflammatory bowel disease (IBD) is a chronic disorder of the gastrointestinal tract. Although the etiology and pathogenesis of IBD remain unknown, pro-inflammatory cytokines including IFN-γ play an...

Local blockade of IL-6R signaling induces lung CD4+ T cell apoptosis in a murine model of asthma via regulatory T cells (2007)

Finotto, Susetta, Eigenbrod, Tatjana, Karwot, Roman, Boross, Ildiko, Doganci, Aysefa, Ito, Hiroaki, ...

We previously reported high levels of the soluble form of the IL-6R (sIL-6R) in the airways of asthmatic subjects. Here, we analyzed the IL-6R effects on Th2 cell survival in the lung by locally...

Interleukin-6: discovery of a pleiotropic cytokine (2006)

Kishimoto, Tadamitsu

Abstract In the late 1960s, the essential role played by T cells in antibody production was reported. This led to our hypothesis that certain molecules would have to be released from T cells to...

Anti-interleukin-6 receptor antibody therapy favors adrenal androgen secretion in patients with rheumatoid arthritis: a randomized, double-blind, placebo-controlled study (2006)

Straub, Rainer H., Härle, Peter, Yamana, Seizo, Matsuda, Takemasa, Takasugi, Kiyoshi, Kishimoto, Tadamitsu, ...

OBJECTIVE: Proinflammatory cytokines such as tumor necrosis factor (TNF) were demonstrated to inhibit adrenal steroidogenesis in patients with rheumatoid arthritis (RA), and this was particularly...

STAT3 mediates cardioprotection against ischemia/reperfusion injury through metallothionein induction in the heart (2005)

Oshima, Yuichi, Fujio, Yasushi, Nakanishi, Tsuyoshi, Itoh, Norio, Yamamoto, Yasuhiro, Negoro, Shinji, ...

Objective: Activation of signal transducer and activator of transcription 3 (STAT3) was reported to be correlated with myocardial protection against ischemia/reperfusion (I/R) injury in ischemic...

Hypermethylation-associated Inactivation of the SOCS-1 Gene, a JAK/STAT Inhibitor, in Human Pancreatic Cancers (2004)

Komazaki, Toshiaki, Nagai, Hisaki, Emi, Mitsuru, Terada, Yoshie, Yabe, Aya, Jin, Enjing, ...

Background: SOCS-1, a JAK-binding protein (SSI-1/SOCS-1/JAB), regulates the JAK/STAT signal transduction pathway that relays signals from various cytokines in the extracellular matrix into the cell....

SOCS-1 suppresses TNF-{alpha}-induced apoptosis through the regulation of Jak activation (2004)

Kimura, Akihiro, Naka, Tetsuji, Nagata, Shigekazu, Kawase, Ichiro, Kishimoto, Tadamitsu

Suppressor of cytokine signaling‐1 (SOCS‐1) was identified as one of the negative feedback regulators of Janus kinase...

Inadequate induction of suppressor of cytokine signaling-1 causes systemic autoimmune diseases (2004)

Fujimoto, Minoru, Tsutsui, Hiroko, Xinshou, Ouyang, Tokumoto, Masanori, Watanabe, Dai, Shima, Yoshihito, ...

Suppressor of cytokine signaling (SOCS)‐1 is a cytokine‐inducible, negative regulatory molecule of Janus kinases (JAK) and its deficiency causes hyper‐response to various cytokines....

The paradigm of IL-6: from basic science to medicine (2002)

Naka, Tetsuji, Nishimoto, Norihiro, Kishimoto, Tadamitsu

Chapter summary IL-6 is a pleiotropic cytokine with a wide range of biological activities in immune regulation, hematopoiesis, inflammation, and oncogenesis. Its activities are shared by IL-6-related...

Joint disease caused by defective gp130-mediated STAT signaling (2002)

Naka, Tetsuji, Kishimoto, Tadamitsu

Abstract IL-6 is a multifunctional cytokine produced by lymphoid and nonlymphoid cells; it regulates immune responses, acute-phase reactions, and inflammation. IL-6 signaling is mediated exclusively...

A regulatory role for suppressor of cytokine signaling-1 in Th polarization in vivo (2002)

Fujimoto, Minoru, Tsutsui, Hiroko, Yumikura-Futatsugi, Shizue, Ueda, Haruyasu, Xingshou, Ouyang, Abe, Tatsuo, ...

Suppressor of cytokine signaling (SOCS)‐1 is an inhibitory molecule for JAK, and its deficiency in mice leads to lymphocyte‐dependent multi‐organ disease and perinatal death. Crossing...

Activation of JAK/STAT pathway transduces cytoprotective signal in rat acute myocardial infarction (2000)

Negoro, Shinji, Kunisada, Keita, Tone, Eiroh, Funamoto, Masanobu, Oh, Hidemasa, Kishimoto, Tadamitsu, ...

Objectives: We reported that the activation of gp130 transduced hypertrophic and cytoprotective signals via Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway in cardiac...

Induction of interleukin (IL)-6 by hypoxia is mediated by nuclear factor (NF)-{kappa}B and NF-IL6 in cardiac myocytes (1999)

Matsui, Hideo, Ihara, Yoshiji, Fujio, Yasushi, Kunisada, Keita, Akira, Sizuo, Kishimoto, Tadamitsu, ...

Objectives: We have previously reported that interleukin (IL)-6 is induced by hypoxic stimulation in cardiac myocytes. In the present study, we examined the induction of potent transcription factors...

The soluble form of the IL-6 receptor (sIL-6R{alpha}) is a potent growth factor for AIDS-associated Kaposi's sarcoma (KS) cells; the soluble form of gp130 is antagonistic for sIL-6R{alpha}-induced AIDS-KS cell growth (1996)

Murakami-Morl, Kaoru, Taga, Tetsuya, Kishimoto, Tadamitsu, Nakamura, Shuji, Takatsu, K

Kaposi's sarcoma (KS) is most frequently associated with HIV-intected individuals (AIDS-KS). While AIDS-KS-derived spindle cells (AIDS-KS cells) contribute to the development of KS lesions, growth...

The genomic structure and chromosomal localization of the mouse STAT3 gene (1996)

Shi, Wei, Inoue, Masahiro, Minami, Masashi, Takeda, Kiyoshi, Matsumoto, Makoto, Matsuda, Yoichi, ...

A variety of cytokines Induce the tyrosine phosphorylation of signal transducers and activators of transcription (STATs). Activation of the same STAT proteins by distinct cytokines and activation of...

Profound reduction of mature B cell numbers, reactivities and serum lg levels in mice which simultaneously carry the XID and CD40 deficiency gense (1996)

Oka, Yoshiro, Rolink, Antonius G., Andersson, Jan, Kamanaka, Masahito, Uchida, Junji, Yasui, Teruhito, ...

It has been known for some time that single mutant nude or CD40T mice have apparently normal numbers of cells in the precursor compartments of bone marrow and the mature B cell compartments of the...

Abnormal distribution of IL-6 receptor in aged MRL/lpr mice: elevated expression on B cells and absence on CD4+ cells (1992)

Kobayashi, Ichiro, Matsuda, Tadashi, Saito, Takashi, Yasukawa, Kiyoshi, Kikutani, Hitoshi, Hirano, Toshio, ...

A mAb against murlne IL-6 receptor (IL-6R), KMH7, was obtained by immunization of hamster with recombinant soluble murlne IL-6R. Flow cytometry analysis of IL-6R distribution on lymphocytes in...

Expression of the CD2 molecule on human B lymphoid progenitors (1992)

Muraguchi, Atsushi, Kawamura, Nobuaki, Hori, Akira, Horii, Yasuhiro, Ichigi, Yasuhisa, Kimoto, Masao, ...

CD2 expression on human B lymphoid progenitor cells was examined. By Immunofluorescence analysis, a small fraction of bone marrow B cells was found to express CD2 on their surface. CD2 expression was...

Age-associated increase in interleukin 6 in MRL/lpr mice (1991)

Tang, Bo, Matsuda, Tadashl, Akira, Shizuo, Nagata, Norikazu, Ikehara, Susumu, Hirano, Toshio, ...

It has been demonstrated that abnormal expression of Interleukin 6 (IL-6) may be Involved In the pathogenesls of a variety of autoimmune diseases and glomerulonephrltls. In this study, we demonstrate...

Differential Effects of IL-2 and IL-6 on the Development of Three Distinct Precursor T-Cell Populations in the Thymus (1990)

Naoko Nakano, Hitoshi Kikutani, Tadamitsu Kishimoto

Three distinct T-cell precursors: bone marrow cells that express low levels of the Thy-1 antigen but no lineage markers (Thy-1-lo/BM); CD4-, CD8-, and CD3- thymocytes that express low levels of the...

Purification and Characterization of Soluble Human IL-6 Receptor Expressed in CHO Cells (1990)

Yasukawa, Kiyoshi, Saito, Takashi, Fukunaga, Takeshi, Sekimori, Yasuo, Koishihara, Yasuo, Fukui, Hiroyasu, ...

An immunosorbent assay system to detect genetically engineered IL-6 receptor (IL-6R) was established, whereby soluble IL-6 receptor (sEL-6R) was detected in the culture medium when sIL-6R cDNA was...

Development of autoimmune insulitis is prevented in E{alpha}d but not in A{beta}k NOD transgenic mice (1989)

Uehira, Masahiro, Uno, Masashi, Kürner, Thomas, Kikutani, Hitoshi, Mori, Koh-ichi, Inomoto, Takeaki, ...

Two lines of Eαd-expressing NOD mice were established by continuously backcrosslng [Eαd B6 transgenic mice × NOD] F1 to parental NOD or directly microinjecting the Eαd gene into fertilized NOD...

High-Level Expression of Human BSF-2/IL-6 cDNA in Escherichia coli Using a New Type of Expression-Preparation System (1988)

Tonouchi, Naoto, Oouchi, Naoki, Kashima, Nobukazu, Kawai, Misako, Nagase, Kazuo, Okano, Akira, ...

BSF-2 (B cell stimulatory factor-2/IL-6) is a member of the lymphokine family and responsible for B celldifferentiation. Expression plasmids of human BSF-2 cDNA were constructed using a trp...

Introduction of Human {gamma}1 Immunoglobulin Genes into Fertilized Mouse Eggs (1984)

YAMAMURA, Ken-ichi, KIKUTANI, Hitoshi, TAKAHASHI, Naoki, TAGA, Tetsuya, AKIRA, Shizuo, KAWAI, Kazuhiko, ...

A rearranged human γ1 immunoglobulin gene was introduced into fertilized mouse eggs. The phage Ch4A-VCE-γ1 was constructed by ligating an EcoRI and BglII fragment of pBR322-CESSV(CE-l) containing...

The D-JH complex is an intermediate to the complete immunoglobulin beavy-chain V-region gene (1983)

Yaoita, Yoshio, Matsunami, Norisada, Yong Choi, Cha, Sugiyama, Haruo, Kishimoto, Tadamitsu, Honjo, Tasuku

We have examined the organization of the immunoglobulin JH segments in three clones derived from a single Abelson murine leukemia virus-transformed cell. Cloning and nucleotide sequence analyses of...

Impairment of antigen-specific antibody production in transgenic mice expressing a dominant-negative form of gp130

Kumanogoh, Atsushi, Marukawa, Satoko, Kumanogoh, Takayuki, Hirota, Hisao, Yoshida, Kenji, Lee, Ihn-Sook, ...

gp130 is a common signal-transducing receptor component for the interleukin 6 family of cytokines functioning in, for example, immune, hematopoietic, and nervous systems. In this study, to...

Targeted disruption of the mouse Stat3 gene leads to early embryonic lethality

Takeda, Kiyoshi, Noguchi, Koichi, Shi, Wei, Tanaka, Takashi, Matsumoto, Makoto, Yoshida, Nobuaki, ...

Signal transducer and activator of transcription (STAT) proteins have been shown to mediate biological actions in response to cytokines. Stat3, a member of the STAT family, is activated by a variety...

Interleukin 6 plays a key role in the development of antigen-induced arthritis

Ohshima, Shiro, Saeki, Yukihiko, Mima, Toru, Sasai, Mitsuko, Nishioka, Katsuhiro, Nomura, Shintaro, ...

To investigate the direct role of interleukin (IL) 6 in the development of rheumatoid arthritis, IL-6-deficient (IL-6 −/−) mice were backcrossed for eight generations into C57BL/6 mice, a strain...

Impaired B-lymphopoiesis, myelopoiesis, and derailed cerebellar neuron migration in CXCR4- and SDF-1-deficient mice

Ma, Qing, Jones, Dan, Borghesani, Paul R., Segal, Rosalind A., Nagasawa, Takashi, Kishimoto, Tadamitsu, ...

The chemokine stromal cell-derived factor 1, SDF-1, is an important regulator of leukocyte and hematopoietic precursor migration and pre-B cell proliferation. The receptor for SDF-1, CXCR4, also...

A cell-autonomous requirement for CXCR4 in long-term lymphoid and myeloid reconstitution

Kawabata, Kenji, Ujikawa, Miho, Egawa, Takeshi, Kawamoto, Hiroshi, Tachibana, Kazunobu, Iizasa, Hisashi, ...

Mice lacking the chemokine stromal cell-derived factor/pre-B cell growth stimulating factor or its primary physiological receptor CXCR4 revealed defects in B lymphopoiesis and bone marrow...

Three distinct domains of SSI-1/SOCS-1/JAB protein are required for its suppression of interleukin 6 signaling

Narazaki, Masashi, Fujimoto, Minoru, Matsumoto, Tomoshige, Morita, Yoshiaki, Saito, Hiroshi, Kajita, Tadahiro, ...

Cytokine-inducible protein SSI-1 [signal transducers and activators of transcription (STAT)-induced STAT inhibitor 1, also referred to as SOCS-1 (suppressor of cytokine signaling 1) or JAB (Janus...

Signals transducers and activators of transcription (STAT)-induced STAT inhibitor-1 (SSI-1)/suppressor of cytokine signaling-1 (SOCS-1) suppresses tumor necrosis factor α-induced cell death in fibroblasts

Morita, Yoshiaki, Naka, Tetsuji, Kawazoe, Yoshinori, Fujimoto, Minoru, Narazaki, Masashi, Nakagawa, Reiko, ...

Signal transducers and activators of transcription (STAT)-induced STAT inhibitor-1 [SSI-1; also known as suppressor of cytokine signaling-1 (SOCS-1)] was identified as a negative feedback regulator...

Molecular cloning and characterization of a murine pre-B-cell growth-stimulating factor/stromal cell-derived factor 1 receptor, a murine homolog of the human immunodeficiency virus 1 entry coreceptor fusin

Nagasawa, Takashi, Nakajima, Toshihiro, Tachibana, Kazunobu, Iizasa, Hisashi, Bleul, Conrad C., Yoshie, Osamu, ...

Pre-B-cell growth-stimulating factor/stromal cell-derived factor 1 (PBSF/SDF-1) is a member of the CXC group of chemokines that is initially identified as a bone marrow stromal cell-derived factor...

Signal transducer and activator of transcription 3 in the heart transduces not only a hypertrophic signal but a protective signal against doxorubicin-induced cardiomyopathy

Kunisada, Keita, Negoro, Shinji, Tone, Eiroh, Funamoto, Masanobu, Osugi, Tomoaki, Yamada, Shuichi, ...

The signal transducer and activator of transcription (STAT) 3, a transcriptional factor downstream of several cytokines, is activated by Janus kinase families and plays a pivotal role in cardiac...

Bruton’s tyrosine kinase activity is negatively regulated by Sab, the Btk-SH3 domain-binding protein

Yamadori, Tomoki, Baba, Yoshihiro, Matsushita, Masato, Hashimoto, Shoji, Kurosaki, Mari, Kurosaki, Tomohiro, ...

Bruton’s tyrosine kinase (Btk) is a cytoplasmic tyrosine kinase that is crucial for human and murine B cell development, and its deficiency causes human X-linked agammaglobulinemia and murine...

Accelerated apoptosis of lymphocytes by augmented induction of Bax in SSI-1 (STAT-induced STAT inhibitor-1) deficient mice

Naka, Tetsuji, Matsumoto, Tomoshige, Narazaki, Masashi, Fujimoto, Minoru, Morita, Yoshiaki, Ohsawa, Yoshiyuki, ...

Growth, differentiation, and programmed cell death (apoptosis) are mainly controlled by cytokines. The Janus kinase–signal transducers and activators of transcription (JAK-STAT) signal pathway is...

BLNK mediates Syk-dependent Btk activation

Baba, Yoshihiro, Hashimoto, Shoji, Matsushita, Masato, Watanabe, Dai, Kishimoto, Tadamitsu, Kurosaki, Tomohiro, ...

Btk is a critical molecule in B cell antigen receptor (BCR)-coupled signaling, and its activity is regulated by Lyn and Syk. Although the molecular mechanism of Lyn-dependent Btk activation has been...

BMP2-mediated alteration in the developmental pathway of fetal mouse brain cells from neurogenesis to astrocytogenesis

Nakashima, Kinichi, Takizawa, Takumi, Ochiai, Wataru, Yanagisawa, Makoto, Hisatsune, Tatsuhiro, Nakafuku, Masato, ...

We show that when telencephalic neural progenitors are briefly exposed to bone morphogenetic protein 2 (BMP2) in culture, their developmental fate is changed from neuronal cells to astrocytic cells....

IL-6 transgenic mouse model for extraosseous plasmacytoma

Kovalchuk, Alexander L., Kim, Joong Su, Park, Sung Sup, Coleman, Allen E., Ward, Jerrold M., Morse, Herbert C., ...

Plasma cell neoplasms in humans comprise plasma cell myeloma, otherwise known as multiple myeloma, Ig deposition and heavy chain diseases, and plasmacytoma (PCT). A subset of PCT, designated...

Joint disease caused by defective gp130-mediated STAT signaling

Naka, Tetsuji, Kishimoto, Tadamitsu

IL-6 is a multifunctional cytokine produced by lymphoid and nonlymphoid cells; it regulates immune responses, acute-phase reactions, and inflammation. IL-6 signaling is mediated exclusively by the...

Expression of the suppressor of cytokine signaling-5 (SOCS5) negatively regulates IL-4-dependent STAT6 activation and Th2 differentiation

Seki, Yoh-ichi, Hayashi, Katsuhiko, Matsumoto, Akira, Seki, Noriyasu, Tsukada, Jun, Ransom, John, ...

The development of helper T (Th) cell subsets, which secrete distinct cytokines, plays an important role in determining the type of immune response. The IL-4-mediated Janus kinase–signal transducer...

Impaired colonization of the gonads by primordial germ cells in mice lacking a chemokine, stromal cell-derived factor-1 (SDF-1)

Ara, Toshiaki, Nakamura, Yuri, Egawa, Takeshi, Sugiyama, Tatsuki, Abe, Kuniya, Kishimoto, Tadamitsu, ...

Primordial germ cells (PGCs) are the founders of sperm or oocytes. PGCs migrate through the tissues of the embryos and colonize the gonads during development. However, the cytokines essential for...

The IL-6R α chain controls lung CD4+CD25+ Treg development and function during allergic airway inflammation in vivo

Doganci, Aysefa, Eigenbrod, Tatjana, Krug, Norbert, De Sanctis, George T., Hausding, Michael, Erpenbeck, Veit J., ...

The cytokine IL-6 acts via a specific receptor complex that consists of the membrane-bound IL-6 receptor (mIL-6R) or the soluble IL-6 receptor (sIL-6R) and glycoprotein 130 (gp130). In this study, we...

Suppressor of cytokine signaling-1 selectively inhibits LPS-induced IL-6 production by regulating JAK–STAT

Kimura, Akihiro, Naka, Tetsuji, Muta, Tatsushi, Takeuchi, Osamu, Akira, Shizuo, Kawase, Ichiro, ...

Suppressor of cytokine signaling-1 (SOCS-1) is one of the negative-feedback regulators of Janus kinase (JAK)–signal transducer and activator of transcription (STAT) signaling. We previously showed...

Impairment of antigen-specific antibody production in transgenic mice expressing a dominant-negative form of gp130

Kumanogoh, Atsushi, Marukawa, Satoko, Kumanogoh, Takayuki, Hirota, Hisao, Yoshida, Kenji, Lee, Ihn-Sook, ...

gp130 is a common signal-transducing receptor component for the interleukin 6 family of cytokines functioning in, for example, immune, hematopoietic, and nervous systems. In this study, to...

Targeted disruption of the mouse Stat3 gene leads to early embryonic lethality

Takeda, Kiyoshi, Noguchi, Koichi, Shi, Wei, Tanaka, Takashi, Matsumoto, Makoto, Yoshida, Nobuaki, ...

Signal transducer and activator of transcription (STAT) proteins have been shown to mediate biological actions in response to cytokines. Stat3, a member of the STAT family, is activated by a variety...

Interleukin 6 plays a key role in the development of antigen-induced arthritis

Ohshima, Shiro, Saeki, Yukihiko, Mima, Toru, Sasai, Mitsuko, Nishioka, Katsuhiro, Nomura, Shintaro, ...

To investigate the direct role of interleukin (IL) 6 in the development of rheumatoid arthritis, IL-6-deficient (IL-6 −/−) mice were backcrossed for eight generations into C57BL/6 mice, a strain...

Impaired B-lymphopoiesis, myelopoiesis, and derailed cerebellar neuron migration in CXCR4- and SDF-1-deficient mice

Ma, Qing, Jones, Dan, Borghesani, Paul R., Segal, Rosalind A., Nagasawa, Takashi, Kishimoto, Tadamitsu, ...

The chemokine stromal cell-derived factor 1, SDF-1, is an important regulator of leukocyte and hematopoietic precursor migration and pre-B cell proliferation. The receptor for SDF-1, CXCR4, also...

A cell-autonomous requirement for CXCR4 in long-term lymphoid and myeloid reconstitution

Kawabata, Kenji, Ujikawa, Miho, Egawa, Takeshi, Kawamoto, Hiroshi, Tachibana, Kazunobu, Iizasa, Hisashi, ...

Mice lacking the chemokine stromal cell-derived factor/pre-B cell growth stimulating factor or its primary physiological receptor CXCR4 revealed defects in B lymphopoiesis and bone marrow...

Three distinct domains of SSI-1/SOCS-1/JAB protein are required for its suppression of interleukin 6 signaling

Narazaki, Masashi, Fujimoto, Minoru, Matsumoto, Tomoshige, Morita, Yoshiaki, Saito, Hiroshi, Kajita, Tadahiro, ...

Cytokine-inducible protein SSI-1 [signal transducers and activators of transcription (STAT)-induced STAT inhibitor 1, also referred to as SOCS-1 (suppressor of cytokine signaling 1) or JAB (Janus...

Signals transducers and activators of transcription (STAT)-induced STAT inhibitor-1 (SSI-1)/suppressor of cytokine signaling-1 (SOCS-1) suppresses tumor necrosis factor α-induced cell death in fibroblasts

Morita, Yoshiaki, Naka, Tetsuji, Kawazoe, Yoshinori, Fujimoto, Minoru, Narazaki, Masashi, Nakagawa, Reiko, ...

Signal transducers and activators of transcription (STAT)-induced STAT inhibitor-1 [SSI-1; also known as suppressor of cytokine signaling-1 (SOCS-1)] was identified as a negative feedback regulator...

Molecular cloning and characterization of a murine pre-B-cell growth-stimulating factor/stromal cell-derived factor 1 receptor, a murine homolog of the human immunodeficiency virus 1 entry coreceptor fusin

Nagasawa, Takashi, Nakajima, Toshihiro, Tachibana, Kazunobu, Iizasa, Hisashi, Bleul, Conrad C., Yoshie, Osamu, ...

Pre-B-cell growth-stimulating factor/stromal cell-derived factor 1 (PBSF/SDF-1) is a member of the CXC group of chemokines that is initially identified as a bone marrow stromal cell-derived factor...

Signal transducer and activator of transcription 3 in the heart transduces not only a hypertrophic signal but a protective signal against doxorubicin-induced cardiomyopathy

Kunisada, Keita, Negoro, Shinji, Tone, Eiroh, Funamoto, Masanobu, Osugi, Tomoaki, Yamada, Shuichi, ...

The signal transducer and activator of transcription (STAT) 3, a transcriptional factor downstream of several cytokines, is activated by Janus kinase families and plays a pivotal role in cardiac...

Bruton’s tyrosine kinase activity is negatively regulated by Sab, the Btk-SH3 domain-binding protein

Yamadori, Tomoki, Baba, Yoshihiro, Matsushita, Masato, Hashimoto, Shoji, Kurosaki, Mari, Kurosaki, Tomohiro, ...

Bruton’s tyrosine kinase (Btk) is a cytoplasmic tyrosine kinase that is crucial for human and murine B cell development, and its deficiency causes human X-linked agammaglobulinemia and murine...

Accelerated apoptosis of lymphocytes by augmented induction of Bax in SSI-1 (STAT-induced STAT inhibitor-1) deficient mice

Naka, Tetsuji, Matsumoto, Tomoshige, Narazaki, Masashi, Fujimoto, Minoru, Morita, Yoshiaki, Ohsawa, Yoshiyuki, ...

Growth, differentiation, and programmed cell death (apoptosis) are mainly controlled by cytokines. The Janus kinase–signal transducers and activators of transcription (JAK-STAT) signal pathway is...

BLNK mediates Syk-dependent Btk activation

Baba, Yoshihiro, Hashimoto, Shoji, Matsushita, Masato, Watanabe, Dai, Kishimoto, Tadamitsu, Kurosaki, Tomohiro, ...

Btk is a critical molecule in B cell antigen receptor (BCR)-coupled signaling, and its activity is regulated by Lyn and Syk. Although the molecular mechanism of Lyn-dependent Btk activation has been...

BMP2-mediated alteration in the developmental pathway of fetal mouse brain cells from neurogenesis to astrocytogenesis

Nakashima, Kinichi, Takizawa, Takumi, Ochiai, Wataru, Yanagisawa, Makoto, Hisatsune, Tatsuhiro, Nakafuku, Masato, ...

We show that when telencephalic neural progenitors are briefly exposed to bone morphogenetic protein 2 (BMP2) in culture, their developmental fate is changed from neuronal cells to astrocytic cells....

IL-6 transgenic mouse model for extraosseous plasmacytoma

Kovalchuk, Alexander L., Kim, Joong Su, Park, Sung Sup, Coleman, Allen E., Ward, Jerrold M., Morse, Herbert C., ...

Plasma cell neoplasms in humans comprise plasma cell myeloma, otherwise known as multiple myeloma, Ig deposition and heavy chain diseases, and plasmacytoma (PCT). A subset of PCT, designated...

Joint disease caused by defective gp130-mediated STAT signaling

Naka, Tetsuji, Kishimoto, Tadamitsu

IL-6 is a multifunctional cytokine produced by lymphoid and nonlymphoid cells; it regulates immune responses, acute-phase reactions, and inflammation. IL-6 signaling is mediated exclusively by the...

Expression of the suppressor of cytokine signaling-5 (SOCS5) negatively regulates IL-4-dependent STAT6 activation and Th2 differentiation

Seki, Yoh-ichi, Hayashi, Katsuhiko, Matsumoto, Akira, Seki, Noriyasu, Tsukada, Jun, Ransom, John, ...

The development of helper T (Th) cell subsets, which secrete distinct cytokines, plays an important role in determining the type of immune response. The IL-4-mediated Janus kinase–signal transducer...

Impaired colonization of the gonads by primordial germ cells in mice lacking a chemokine, stromal cell-derived factor-1 (SDF-1)

Ara, Toshiaki, Nakamura, Yuri, Egawa, Takeshi, Sugiyama, Tatsuki, Abe, Kuniya, Kishimoto, Tadamitsu, ...

Primordial germ cells (PGCs) are the founders of sperm or oocytes. PGCs migrate through the tissues of the embryos and colonize the gonads during development. However, the cytokines essential for...

The IL-6R α chain controls lung CD4+CD25+ Treg development and function during allergic airway inflammation in vivo

Doganci, Aysefa, Eigenbrod, Tatjana, Krug, Norbert, De Sanctis, George T., Hausding, Michael, Erpenbeck, Veit J., ...

The cytokine IL-6 acts via a specific receptor complex that consists of the membrane-bound IL-6 receptor (mIL-6R) or the soluble IL-6 receptor (sIL-6R) and glycoprotein 130 (gp130). In this study, we...

Suppressor of cytokine signaling-1 selectively inhibits LPS-induced IL-6 production by regulating JAK–STAT

Kimura, Akihiro, Naka, Tetsuji, Muta, Tatsushi, Takeuchi, Osamu, Akira, Shizuo, Kawase, Ichiro, ...

Suppressor of cytokine signaling-1 (SOCS-1) is one of the negative-feedback regulators of Janus kinase (JAK)–signal transducer and activator of transcription (STAT) signaling. We previously showed...

IL-6-dependent and -independent pathways in the development of interleukin 17-producing T helper cells

Kimura, Akihiro, Naka, Tetsuji, Kishimoto, Tadamitsu

CD4+ T cells producing IL-17 [T helper (Th)17], as distinct from Th1 or Th2 cells, have recently been shown to be associated with autoimmunity, but it is not entirely clear how Th17 cells are...

Differential Effects of IL-2 and IL-6 on the Development of Three Distinct Precursor T-Cell Populations in the Thymus

Nakano, Naoko, Kikutani, Hitoshi, Kishimoto, Tadamitsu

Three distinct T-cell precursors: bone marrow cells that express low levels of the Thy-1 antigen but no lineage markers (Thy-1-lo/BM); CD4-, CD8-, and CD3- thymocytes that express low levels of the...

CXCR4/fusin Is Not a Species-specific Barrier in Murine Cells for HIV-1 Entry

Tachibana, Kazunobu, Nakajima, Toshihiro, Sato, Akihiko, Igarashi, Kenji, Shida, Hisatoshi, Iizasa, Hisashi, ...

Since some murine cells expressing human CD4 fail to internalize HIV-1, another block was thought to be located at the level of viral entry in addition to CD4. Recently, CXCR4 was shown to function...

A Small Molecule CXCR4 Inhibitor that Blocks T Cell Line–tropic HIV-1 Infection

Murakami, Tsutomu, Nakajima, Toshihiro, Koyanagi, Yoshio, Tachibana, Kazunobu, Fujii, Nobutaka, Tamamura, Hirokazu, ...

Several members of the chemokine receptor family have been shown to function in association with CD4 to permit human immunodeficiency virus type 1 (HIV-1) entry and infection. The CXC chemokine...

Postnatally Induced Inactivation of gp130 in Mice Results in Neurological, Cardiac, Hematopoietic, Immunological, Hepatic, and Pulmonary Defects

Betz, Ulrich A.K., Bloch, Wilhelm, Van Den Broek, Maries, Yoshida, Kanji, Taga, Tetsuya, Kishimoto, Tadamitsu, ...

The pleiotrophic but overlapping functions of the cytokine family that includes interleukin (IL)-6, IL-11, leukemia inhibitory factor, oncostatin M, ciliary neurotrophic factor, and cardiotrophin 1...

IL-6 blockade inhibits the induction of myelin antigen-specific Th17 cells and Th1 cells in experimental autoimmune encephalomyelitis

Serada, Satoshi, Fujimoto, Minoru, Mihara, Masahiko, Koike, Nobuo, Ohsugi, Yoshiyuki, Nomura, Shintaro, ...

The development of Th17 cells is a key event in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), a murine model of human multiple sclerosis (MS). Previous studies have...

Aryl hydrocarbon receptor regulates Stat1 activation and participates in the development of Th17 cells

Kimura, Akihiro, Naka, Tetsuji, Nohara, Keiko, Fujii-Kuriyama, Yoshiaki, Kishimoto, Tadamitsu

IL-17-producing T helper cells (Th17) have been recently identified as a previously undescribed subset of helper T cells. Here, we demonstrate that aryl hydrocarbon receptor (Ahr) has an important...