The Experts below are selected from a list of 23325 Experts worldwide ranked by ideXlab platform
Junichiro Mizuguchi - One of the best experts on this subject based on the ideXlab platform.
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Synergistic antitumor effect by coexpression of Chemokine CCL21/SLC and costimulatory molecule LIGHT
Cancer Gene Therapy, 2004Co-Authors: Masayuki Hisada, Takayuki Yoshimoto, Sadahiro Kamiya, Yasushi Magami, Hiroko Miyaji, Toshihiko Yoneto, Koji Tamada, Yasuhisa Koyanagi, T Aoki, Junichiro MizuguchiAbstract:To establish a more efficient treatment for immunotherapy against solid tumors, we have evaluated the antitumor effect by coexpression of a Chemokine CCL21/secondary lymphoid tissue Chemokine and a costimulatory molecule LIGHT in colon carcinoma C26. C26 cells expressing either CCL21 or LIGHT exhibited a significantly reduced tumor growth in vivo , and mice inoculated with these cells showed a prolonged survival, but eventually all these mice died. In contrast, C26 cells expressing both CCL21 and LIGHT exhibited a minimal tumor growth in vivo , and all these mice survived healthily with a tumor remission and consequently acquired a strong protective immunity. A markedly increased infiltration of mature dendritic cells (DCs), and CD8^+ T cells was observed in the tumor mass, and their spleen cells showed a greatly enhanced cytotoxic T lymphocyte (CTL) activity against C26 tumor and interferon (IFN)-γ production. Neutralization of IFN-γ or depletion of CD8^+ or CD4^+ T cells significantly reduced the antitumor activity. These results suggest that the combined treatment with CCL21 and LIGHT is able to induce a synergistic antitumor effect to eradicate tumor completely by greatly enhancing tumor-infiltration of lymphocytes including mature DCs and CD8^+ T cells, resulting in markedly augmented CTL activity and IFN-γ production.
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synergistic antitumor effect by coexpression of Chemokine CCL21 slc and costimulatory molecule light
Cancer Gene Therapy, 2004Co-Authors: Masayuki Hisada, Takayuki Yoshimoto, Sadahiro Kamiya, Yasushi Magami, Hiroko Miyaji, Toshihiko Yoneto, Koji Tamada, Yasuhisa Koyanagi, T Aoki, Junichiro MizuguchiAbstract:Synergistic antitumor effect by coexpression of Chemokine CCL21/SLC and costimulatory molecule LIGHT
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Synergistic antitumor effect by coexpression of Chemokine CCL21/SLC and costimulatory molecule LIGHT.
Cancer gene therapy, 2004Co-Authors: Masayuki Hisada, Takayuki Yoshimoto, Sadahiro Kamiya, Yasushi Magami, Hiroko Miyaji, Toshihiko Yoneto, Koji Tamada, Aoki T, Yasuhisa Koyanagi, Junichiro MizuguchiAbstract:Synergistic antitumor effect by coexpression of Chemokine CCL21/SLC and costimulatory molecule LIGHT
Sergio A. Lira - One of the best experts on this subject based on the ideXlab platform.
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A Critical Role for Dendritic Cells in the Formation of Lymphatic Vessels within Tertiary Lymphoid Structures
Journal of immunology (Baltimore Md. : 1950), 2011Co-Authors: Luciana R. Muniz, Sergio A. Lira, Michelle E. Pacer, Glaucia C. FurtadoAbstract:Ectopic, or tertiary, lymphoid aggregates often form in chronically inflamed areas. Lymphatic vessels, as well as high endothelial venules, form within these lymphoid aggregates, but the mechanisms underlying their development are poorly understood. Overexpression of the Chemokine CCL21 in the thyroid of transgenic mice leads to formation of lymphoid aggregates containing topologically segregated T and B lymphocytes, dendritic cells (DCs), and specialized vasculature, including Lyve-1+/Prox-1+ lymphatic vessels. In this article, we show that adoptive transfer of mature CD4+ T cells into animals expressing CCL21 in a RAG-deficient background promotes the influx of host NK cells and DCs into the thyroid and the formation of new lymphatic vessels within 10 d. This process is dependent on the expression of lymphotoxin ligands by host cells, but not by the transferred CD4+ T cells. Ablation of host DCs, but not NK cells, reduces the formation of new lymphatic vessels in the thyroid. Taken together, these data suggest a critical role for CD11c+ DCs in the induction of lymphangiogenesis in tertiary lymphoid structures.
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Lymphotoxin β receptor signaling is required for inflammatory lymphangiogenesis in the thyroid
Proceedings of the National Academy of Sciences of the United States of America, 2007Co-Authors: Glaucia C. Furtado, Tatjana Marinkovic, Andrea P. Martin, Alexandre Garin, Benjamin Hoch, Wolfgang Hübner, Benjamin K. Chen, Eric M. Genden, Mihaela Skobe, Sergio A. LiraAbstract:Infiltration of lymphocytes into the thyroid gland and formation of lymph node-like structures is a hallmark of Hashimoto's thyroiditis. Here we demonstrate that lymphatic vessels are present within these infiltrates. Mice overexpressing the Chemokine CCL21 in the thyroid (TGCCL21 mice) developed similar lymphoid infiltrates and lymphatic vessels. TGCCL21 mice lacking mature T and B cells (RAGTGCCL21 mice) did not have cellular infiltrates or increased number of lymphatic vessels compared with controls. Transfer of CD3(+)CD4(+) T cells into RAGTGCCL21 mice promoted the development of LYVE-1(+)podoplanin(+)Prox-1(+) vessels in the thyroid. Genetic deletion of lymphotoxin beta receptor or lymphotoxin alpha abrogated development of lymphatic vessels in the inflamed areas in the thyroid but did not affect development of neighboring lymphatics. These results define a model for the study of inflammatory lymphangiogenesis in the thyroid and implicate lymphotoxin beta receptor signaling in this process.
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Central Nervous System Inflammation and Neurological Disease in Transgenic Mice Expressing the CC Chemokine CCL21 in Oligodendrocytes
Journal of immunology (Baltimore Md. : 1950), 2002Co-Authors: Shu-cheng Chen, Michael W. Leach, Yuetian Chen, Xiao-yan Cai, Lee Sullivan, Maria T. Wiekowski, B. J. Dovey-hartman, Albert Zlotnik, Sergio A. LiraAbstract:To study the biological role of the Chemokine ligands CCL19 and CCL21, we generated transgenic mice expressing either gene in oligodendrocytes of the CNS. While all transgenic mice expressing CCL19 in the CNS developed normally, most (18 of 26) of the CCL21 founder mice developed a neurological disease that was characterized by loss of landing reflex, tremor, and ataxia. These neurological signs were observed as early as postnatal day 9 and were associated with weight loss and death during the first 4 wk of life. Microscopic examination of the brain and spinal cord of CCL21 transgenic mice revealed scattered leukocytic infiltrates that consisted primarily of neutrophils and eosinophils. Additional findings included hypomyelination, spongiform myelinopathy with evidence of myelin breakdown, and reactive gliosis. Thus, ectopic expression of the CC Chemokine CCL21, but not CCL19, induced a significant inflammatory response in the CNS. However, neither Chemokine was sufficient to recruit lymphocytes into the CNS. These observations are in striking contrast to the reported activities of these molecules in vitro and may indicate specific requirements for their biological activity in vivo.
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ectopic expression of the murine Chemokines CCL21a and CCL21b induces the formation of lymph node like structures in pancreas but not skin of transgenic mice
Journal of Immunology, 2002Co-Authors: Shu-cheng Chen, Maria T. Wiekowski, Galya Vassileva, David Kinsley, Sandra Holzmann, Denise Manfra, Nikolaus Romani, Sergio A. LiraAbstract:The CC Chemokine CCL21 is a potent chemoattractant for lymphocytes and dendritic cells in vitro. In the murine genome there are multiple copies of CCL21 encoding two CCL21 proteins that differ from each other by one amino acid at position 65 (either a serine or leucine residue). In this report, we examine the expression pattern and biological activities of both forms of CCL21. We found that although both serine and leucine forms are expressed in most tissues examined, the former was the predominant form in lymphoid organs while the latter was predominantly expressed in nonlymphoid organs. When expressed in transgenic pancreas, both forms of CCL21 were capable of inducing the formation of lymph node-like structures composed primarily of T and B cells and a few dendritic cells. Induction of lymph node-like structures by these CCL21 proteins, however, could not be reproduced in every tissue. For instance, no lymphocyte recruitment or accumulation was observed when CCL21 was overexpressed in the skin. We conclude that both forms of CCL21 protein are biologically equivalent in promoting lymphocyte recruitment to the pancreas, and that their ability to induce the formation of lymph node-like structures is dependent on the tissues in which they are expressed.
Hendrikus Boddeke - One of the best experts on this subject based on the ideXlab platform.
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Secondary lymphoid tissue Chemokine (CCL21) in neuronmicroglia signalling
Brain Behavior and Immunity, 2009Co-Authors: Knut Biber, Eiko K. De Jong, Jonathan Vinet, Hilmar R. J. Van Weering, Hendrikus BoddekeAbstract:Microglia is considered to be the sentinel of the CNS. Accordingly, microglia activity aims to protect and to restore, and only in case of uncontrolled or impaired microglia function, these cells may have detrimental effects. The control of microglia activity is thus an important issue to understand. The family of Chemokines are versatile signals specialized to control cell-cell interactions. Neurons express a variety of Chemokines in a temporarily and spatially regulated manner and microglia respond to these messengers via the appropriate receptors. Here, we would like to discuss the function of CCL21 in the brain. In the peripheral immune system, CCL21 is known as homeostatic Chemokine that is constitutively expressed in secondary lymphoid tissue. CCL21 is important for the development of lymphoid structures and several aspects of the specific immune response. In the brain, CCL21 is specifically expressed in endangered or damaged neurons. Our recent data indicate that neuronal CCL21 is sorted in large-dense core vesicles, transported into neuronal axons, and released in a regulated manner. Microglia in vitro and in situ responds to CCL21 stimulation with calcium signaling and chemotaxis via the Chemokine receptor CXCR3. The activity of microglia in response to neuronal damage (in vitro, in situ, and in vivo) is significantly changed when CCL21-CXCR3 signaling is disturbed. Due to these data we suggest a brain-specific function of CCL21 in directed neuron-microglia communication after neuronal injury.
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Secondary Lymphoid Tissue Chemokine (CCL21) Activates CXCR3 to Trigger a Cl− Current and Chemotaxis in Murine Microglia
Journal of immunology (Baltimore Md. : 1950), 2002Co-Authors: Angelika Rappert, Martin Lipp, Knut Biber, Hendrikus Boddeke, Christiane Nolte, Andreas Schubel, Norma P. Gerard, Craig Gerard, Helmut KettenmannAbstract:Microglial cells represent the major immunocompetent element of the CNS and are activated by any type of brain injury or disease. A candidate for signaling neuronal injury to microglial cells is the CC Chemokine ligand CCL21, given that damaged neurons express CCL21. Investigating microglia in acute slices and in culture, we demonstrate that a local application of CCL21 for 30 s triggered a Cl(-) conductance with lasted for tens of minutes. This response was sensitive to the Cl(-) channel blockers 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid and 4-acetamide-4'-isothiocyanatostilbene, 2,2'-disulfonic acid. Moreover, CCL21 triggered a chemotaxis response, which was sensitive to Cl(-) channel blockers. In microglial cells cultured from CCR7 knockout mice, CCL21 produced the same type of Cl(-) current as well as a chemotaxis response. In contrast, in microglial cells from CXCR3 knockout mice, CCL21 triggered neither a Cl(-) conductance nor a chemotaxis response after CCL21 application. We conclude that the CCL21-induced Cl(-) current is a prerequisite for the chemotaxis response mediated by the activation of CXCR3 but not CCR7 receptors, indicating that in brain CCL21 acts via a different receptor system than in lymphoid organs.
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secondary lymphoid tissue Chemokine CCL21 activates cxcr3 to trigger a cl current and chemotaxis in murine microglia
Journal of Immunology, 2002Co-Authors: Angelika Rappert, Martin Lipp, Knut Biber, Hendrikus Boddeke, Christiane Nolte, Andreas Schubel, Norma P. Gerard, Craig Gerard, Helmut KettenmannAbstract:Microglial cells represent the major immunocompetent element of the CNS and are activated by any type of brain injury or disease. A candidate for signaling neuronal injury to microglial cells is the CC Chemokine ligand CCL21, given that damaged neurons express CCL21. Investigating microglia in acute slices and in culture, we demonstrate that a local application of CCL21 for 30 s triggered a Cl(-) conductance with lasted for tens of minutes. This response was sensitive to the Cl(-) channel blockers 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid and 4-acetamide-4'-isothiocyanatostilbene, 2,2'-disulfonic acid. Moreover, CCL21 triggered a chemotaxis response, which was sensitive to Cl(-) channel blockers. In microglial cells cultured from CCR7 knockout mice, CCL21 produced the same type of Cl(-) current as well as a chemotaxis response. In contrast, in microglial cells from CXCR3 knockout mice, CCL21 triggered neither a Cl(-) conductance nor a chemotaxis response after CCL21 application. We conclude that the CCL21-induced Cl(-) current is a prerequisite for the chemotaxis response mediated by the activation of CXCR3 but not CCR7 receptors, indicating that in brain CCL21 acts via a different receptor system than in lymphoid organs.
Masayuki Hisada - One of the best experts on this subject based on the ideXlab platform.
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Synergistic antitumor effect by coexpression of Chemokine CCL21/SLC and costimulatory molecule LIGHT
Cancer Gene Therapy, 2004Co-Authors: Masayuki Hisada, Takayuki Yoshimoto, Sadahiro Kamiya, Yasushi Magami, Hiroko Miyaji, Toshihiko Yoneto, Koji Tamada, Yasuhisa Koyanagi, T Aoki, Junichiro MizuguchiAbstract:To establish a more efficient treatment for immunotherapy against solid tumors, we have evaluated the antitumor effect by coexpression of a Chemokine CCL21/secondary lymphoid tissue Chemokine and a costimulatory molecule LIGHT in colon carcinoma C26. C26 cells expressing either CCL21 or LIGHT exhibited a significantly reduced tumor growth in vivo , and mice inoculated with these cells showed a prolonged survival, but eventually all these mice died. In contrast, C26 cells expressing both CCL21 and LIGHT exhibited a minimal tumor growth in vivo , and all these mice survived healthily with a tumor remission and consequently acquired a strong protective immunity. A markedly increased infiltration of mature dendritic cells (DCs), and CD8^+ T cells was observed in the tumor mass, and their spleen cells showed a greatly enhanced cytotoxic T lymphocyte (CTL) activity against C26 tumor and interferon (IFN)-γ production. Neutralization of IFN-γ or depletion of CD8^+ or CD4^+ T cells significantly reduced the antitumor activity. These results suggest that the combined treatment with CCL21 and LIGHT is able to induce a synergistic antitumor effect to eradicate tumor completely by greatly enhancing tumor-infiltration of lymphocytes including mature DCs and CD8^+ T cells, resulting in markedly augmented CTL activity and IFN-γ production.
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synergistic antitumor effect by coexpression of Chemokine CCL21 slc and costimulatory molecule light
Cancer Gene Therapy, 2004Co-Authors: Masayuki Hisada, Takayuki Yoshimoto, Sadahiro Kamiya, Yasushi Magami, Hiroko Miyaji, Toshihiko Yoneto, Koji Tamada, Yasuhisa Koyanagi, T Aoki, Junichiro MizuguchiAbstract:Synergistic antitumor effect by coexpression of Chemokine CCL21/SLC and costimulatory molecule LIGHT
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Synergistic antitumor effect by coexpression of Chemokine CCL21/SLC and costimulatory molecule LIGHT.
Cancer gene therapy, 2004Co-Authors: Masayuki Hisada, Takayuki Yoshimoto, Sadahiro Kamiya, Yasushi Magami, Hiroko Miyaji, Toshihiko Yoneto, Koji Tamada, Aoki T, Yasuhisa Koyanagi, Junichiro MizuguchiAbstract:Synergistic antitumor effect by coexpression of Chemokine CCL21/SLC and costimulatory molecule LIGHT
Horacio M. Serra - One of the best experts on this subject based on the ideXlab platform.
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Up-regulation of the Chemokine CCL21 in the skin of subjects exposed to irritants
BMC immunology, 2004Co-Authors: Yanina Eberhard, Alejandro Ruiz Lascano, Susana G. Ortiz, Raquel Kuznitzky, Horacio M. SerraAbstract:Background Expression of murine CCL21 by dermal lymphatic endothelial cells (LEC) has been demonstrated to be one of the most important steps in Langerhans cell emigration from skin. Previously, our group and others have found that this Chemokine is up-regulated in different human inflammatory skin diseases mediated by diverse specific immune responses. This study was carried out to investigate the involvement of CCL21 in human skin after challenge with irritant agents responsible for inducing Irritant Contact Dermatitis (ICD).
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Secondary lymphoid tissue Chemokine (CCL21) is upregulated in allergic contact dermatitis.
International archives of allergy and immunology, 2004Co-Authors: Horacio M. Serra, Yanina Eberhard, Andrea Martin, Norberto Gallino, Julio Gagliardi, C. E. Baena-cagnani, Alejandro Ruiz Lascano, Susana G. Ortiz, Ana Lía Mariani, Mariagrazia UguccioniAbstract:Chemokines are important players in the development of allergic contact dermatitis (ACD). The participation of secondary lymphoid tissue Chemokine (CCL21) is essential in the induction of the disease due to its expression in lymphatic vessels and in secondary lymphoid organs. Since there is no information about its participation during the effector phase of ACD, we studied this Chemokine in patients already diagnosed with ACD, who were challenged with the relevant positive and negative (control) antigens. All patients showed a specific antigen-induced immune response characterized by early expression of inflammatory markers in blood endothelial cells followed by dermal accumulation of mononuclear cells with an important increase in infiltration of CXCR3+ but not of CCR7+ cells. In situ hybridization and immunohistochemistry showed low levels of CCL21 in lymphatic vessels at 2 h, whereas they were significantly increased at 10 and 48 h in all positive patch tests. In contrast, very low expression of this Chemokine was observed in skin biopsies from the control site at 48 h. In addition, Langerin+ cells, which were present in dermis from positive patch tests at 2 h, were diminished in number at 10 and 48 h, but a significant number of those cells was still present in dermal areas of the control site at 48 h. We demonstrate for the first time that CCL21, a constitutively expressed Chemokine, is strongly upregulated in human lymphatic vessels during a Th1/Tc1 allergic inflammatory response. This can provide the signal required for CCR7+ cells to leave the skin through CCL21-positive lymphatic vessels.