The Experts below are selected from a list of 127551 Experts worldwide ranked by ideXlab platform
Shun Ishibashi - One of the best experts on this subject based on the ideXlab platform.
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Interleukin 12p40 gene il 12b polymorphism and type 1 diabetes mellitus in japanese possible role in subjects without having high risk hla haplotypes
Diabetes Research and Clinical Practice, 2006Co-Authors: Jian Mei Yang, Shoichiro Nagasaka, Toshimitsu Yatagai, Tomoatsu Nakamura, Ikuyo Kusaka, San-e Ishikawa, Toshikazu Saito, Shun IshibashiAbstract:The present study was undertaken to clarify a role of Interleukin-12p40 gene (IL-12B) polymorphism, located on chromosome 5q33-34 (IDDM 18), in Japanese subjects with Type 1 diabetes mellitus (T1DM) and autoimmune thyroid diseases (AITD). In 179 subjects with T1DM, 166 with AITD (128 with Graves' disease and 38 with Hashimoto's thyroiditis) and 115 healthy control subjects, the IL-12B 3'UTR A-C polymorphism was determined by PCR-RFLP method. In T1DM subjects, the genotype was also analyzed in relation to human leukocyte antigen (HLA)-DRB1-DQB1 haplotype status. There was a weak difference in the distribution of the genotype frequency between T1DM and control subjects, and the C allele frequency was higher in T1DM subjects (P<0.05). In 68 T1DM subjects without having high-risk HLA haplotypes to T1DM in this population, the genotype distribution and C allele frequency was significantly different from control subjects without high-risk HLA haplotypes (P<0.01), and from T1DM subjects with high-risk HLA haplotypes (n=111) (P<0.05). There was no difference in the genotype and allele frequencies between AITD and control subjects. In conclusion, the IL-12B 3'UTR A-C polymorphism did not seem to play a major role on genetic susceptibility to T1DM and AITD in Japanese, although the polymorphism conferred susceptibility in T1DM subjects without having high-risk HLA haplotypes. The IL-12B 3'UTR A-C polymorphism would be considered as a supplementary risk factor to T1DM in conjunction with HLA haplotypes.
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Interleukin-12p40 gene (IL-12B) polymorphism and Type 1 diabetes mellitus in Japanese: possible role in subjects without having high-risk HLA haplotypes.
Diabetes Research and Clinical Practice, 2006Co-Authors: Jian Mei Yang, Shoichiro Nagasaka, Toshimitsu Yatagai, Tomoatsu Nakamura, Ikuyo Kusaka, San-e Ishikawa, Toshikazu Saito, Shun IshibashiAbstract:The present study was undertaken to clarify a role of Interleukin-12p40 gene (IL-12B) polymorphism, located on chromosome 5q33-34 (IDDM 18), in Japanese subjects with Type 1 diabetes mellitus (T1DM) and autoimmune thyroid diseases (AITD). In 179 subjects with T1DM, 166 with AITD (128 with Graves' disease and 38 with Hashimoto's thyroiditis) and 115 healthy control subjects, the IL-12B 3'UTR A-C polymorphism was determined by PCR-RFLP method. In T1DM subjects, the genotype was also analyzed in relation to human leukocyte antigen (HLA)-DRB1-DQB1 haplotype status. There was a weak difference in the distribution of the genotype frequency between T1DM and control subjects, and the C allele frequency was higher in T1DM subjects (P
Jaap T. Van Dissel - One of the best experts on this subject based on the ideXlab platform.
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Genetics, cytokines and human infectious disease: lessons from weakly pathogenic mycobacteria and salmonellae
Nature Genetics, 2002Co-Authors: Tom H.m. Ottenhoff, Frank A.w. Verreck, Elgin G.r. Lichtenauer-kaligis, Marieke A. Hoeve, Ozden Sanal, Jaap T. Van DisselAbstract:Host genetic factors are important in determining the outcome of infections caused by intracellular pathogens, including mycobacteria and salmonellae, but until now have been poorly characterized. Recently, some individuals with severe infections due to otherwise weakly pathogenic mycobacteria (non-tuberculous mycobacteria or Mycobacterium bovis bacille Calmette-Guérin) or Salmonella species have been shown to be unable to produce or respond to interferon-γ. This inability results from mutations in any of five genes encoding essential proteins of the type 1 cytokine cascade: Interleukin-12p40, Interleukin-12Rβ1, interferon-γR1, interferon-γR2 or STAT1. Ten syndromes have thus far been identified. Recent insights in genetically controlled host defense and susceptibility to mycobacterial disease are discussed.
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Genetics, cytokines and human infectious disease: lessons from weakly pathogenic mycobacteria and salmonellae.
Nature Genetics, 2002Co-Authors: Tom H.m. Ottenhoff, Frank A.w. Verreck, Elgin G.r. Lichtenauer-kaligis, Marieke A. Hoeve, Ozden Sanal, Jaap T. Van DisselAbstract:Host genetic factors are important in determining the outcome of infections caused by intracellular pathogens, including mycobacteria and salmonellae, but until now have been poorly characterized. Recently, some individuals with severe infections due to otherwise weakly pathogenic mycobacteria (non-tuberculous mycobacteria or Mycobacterium bovis bacille Calmette-Guerin) or Salmonella species have been shown to be unable to produce or respond to interferon-γ. This inability results from mutations in any of five genes encoding essential proteins of the type 1 cytokine cascade: Interleukin-12p40, Interleukin-12Rβ1, interferon-γR1, interferon-γR2 or STAT1. Ten syndromes have thus far been identified. Recent insights in genetically controlled host defense and susceptibility to mycobacterial disease are discussed.
Tom H.m. Ottenhoff - One of the best experts on this subject based on the ideXlab platform.
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The Same IκBα Mutation in Two Related Individuals Leads to Completely Different Clinical Syndromes
Journal of Experimental Medicine, 2004Co-Authors: Riny Janssen, Marieke A. Hoeve, Annelies Van Wengen, Monique Ten Dam, Miriam Van Der Burg, Jacques J.m. Van Dongen, Esther Van De Vosse, Maarten J. D. Van Tol, Robbert G. M. Bredius, Tom H.m. OttenhoffAbstract:Both innate and adaptive immune responses are dependent on activation of nuclear factor κB (NF-κB), induced upon binding of pathogen-associated molecular patterns to Toll-like receptors (TLRs). In murine models, defects in NF-κB pathway are often lethal and viable knockout mice have severe immune defects. Similarly, defects in the human NF-κB pathway described to date lead to severe clinical disease. Here, we describe a patient with a hyper immunoglobulin M–like immunodeficiency syndrome and ectodermal dysplasia. Monocytes did not produce Interleukin 12p40 upon stimulation with various TLR stimuli and nuclear translocation of NF-κB was impaired. T cell receptor–mediated proliferation was also impaired. A heterozygous mutation was found at serine 32 in IκBα. Interestingly, his father has the same mutation but displays complex mosaicism. He does not display features of ectodermal dysplasia and did not suffer from serious infections with the exception of a relapsing Salmonella typhimurium infection. His monocyte function was impaired, whereas T cell function was relatively normal. Consistent with this, his T cells almost exclusively displayed the wild-type allele, whereas both alleles were present in his monocytes. We propose that the T and B cell compartment of the mosaic father arose as a result of selection of wild-type cells and that this underlies the widely different clinical phenotype.
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Genetics, cytokines and human infectious disease: lessons from weakly pathogenic mycobacteria and salmonellae
Nature Genetics, 2002Co-Authors: Tom H.m. Ottenhoff, Frank A.w. Verreck, Elgin G.r. Lichtenauer-kaligis, Marieke A. Hoeve, Ozden Sanal, Jaap T. Van DisselAbstract:Host genetic factors are important in determining the outcome of infections caused by intracellular pathogens, including mycobacteria and salmonellae, but until now have been poorly characterized. Recently, some individuals with severe infections due to otherwise weakly pathogenic mycobacteria (non-tuberculous mycobacteria or Mycobacterium bovis bacille Calmette-Guérin) or Salmonella species have been shown to be unable to produce or respond to interferon-γ. This inability results from mutations in any of five genes encoding essential proteins of the type 1 cytokine cascade: Interleukin-12p40, Interleukin-12Rβ1, interferon-γR1, interferon-γR2 or STAT1. Ten syndromes have thus far been identified. Recent insights in genetically controlled host defense and susceptibility to mycobacterial disease are discussed.
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Genetics, cytokines and human infectious disease: lessons from weakly pathogenic mycobacteria and salmonellae.
Nature Genetics, 2002Co-Authors: Tom H.m. Ottenhoff, Frank A.w. Verreck, Elgin G.r. Lichtenauer-kaligis, Marieke A. Hoeve, Ozden Sanal, Jaap T. Van DisselAbstract:Host genetic factors are important in determining the outcome of infections caused by intracellular pathogens, including mycobacteria and salmonellae, but until now have been poorly characterized. Recently, some individuals with severe infections due to otherwise weakly pathogenic mycobacteria (non-tuberculous mycobacteria or Mycobacterium bovis bacille Calmette-Guerin) or Salmonella species have been shown to be unable to produce or respond to interferon-γ. This inability results from mutations in any of five genes encoding essential proteins of the type 1 cytokine cascade: Interleukin-12p40, Interleukin-12Rβ1, interferon-γR1, interferon-γR2 or STAT1. Ten syndromes have thus far been identified. Recent insights in genetically controlled host defense and susceptibility to mycobacterial disease are discussed.
Zhe-xiong Lian - One of the best experts on this subject based on the ideXlab platform.
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CD8+ T cells and IFN-γ induce autoimmune myelofibrosis in mice.
Journal of Autoimmunity, 2018Co-Authors: Yuan Yao, Shu-han Yang, Cai-yue Gao, Liang-huan Liao, Yu-qing Xie, Xue-ying Yin, Yan-qing Yang, Yun-yun Fei, Zhe-xiong LianAbstract:Abstract Myelofibrosis usually occurs either as a part of a myelodysplastic syndrome or in conjunction with neoplasia. It is not commonly thought of an autoimmune disease. We reported that p40−/−IL-2Rα−/− (Interleukin-12p40 and Interleukin-2 receptor alpha double knockout) mice, a mouse model of human primary biliary cholangitis, exhibited features consistent with autoimmune myelofibrosis, including anemia associated with bone marrow fibrosis, and extramedullary hematopoiesis (EMH) including LSK (Lineage-c-Kit+Sca-1+) cells in spleen, liver and peripheral blood. There were also increased LSK cells in bone marrow but they demonstrated impaired hematopoiesis. Importantly effector memory T cells that infiltrated the bone marrow of p40−/−IL-2Rα−/− mice manifested a higher ability to produce IFN-γ. CD8+ T cells, already known to play a dominate role in portal inflammation, were also key for bone marrow dysregulation and EMH. IFN-γ was the key cytokine that induced bone marrow fibrosis, bone marrow failure and EMH. Finally anti-CD8α antibody therapy fully protected p40−/−IL-2Rα−/− mice from autoimmune myelofibrosis. In conclusion, our results demonstrate that CD8+ T cells and IFN-γ are associated with autoimmune myelofibrosis, a finding that may allow targeting of CD8+ T cells and IFN-γ as a therapeutic targets.
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deletion of Interleukin 12p40 suppresses autoimmune cholangitis in dominant negative transforming growth factor β receptor type ii mice
Hepatology, 2009Co-Authors: Katsunori Yoshida, Guo-xiang Yang, Weici Zhang, Masanobu Tsuda, Koichi Tsuneyama, Yuki Moritoki, Aftab A. Ansari, Kazuichi Okazaki, Zhe-xiong Lian, Ross L. CoppelAbstract:Our laboratory has reported that mice that express a dominant negative form of transforming growth factor-β receptor restricted to T cells (dnTGFβRII) develop an inflammatory biliary ductular disease with raised serum levels of IL-12p40 and other proinflammatory cytokines and anti-mitochondrial autoantibodies (AMA), closely resembling human primary biliary cirrhosis (PBC). We have utilized this mouse model to address the potential mechanisms of immune modulation of the liver disease by creating two unique genetic strains, IL-12p40 KO-dnTGFβRII mice and IFN-γ KO-dnTGFβRII mice. The two colonies of genetically modified mice and, for purposes of controls the dnTGFβRII mice, were monitored for liver immunopathology, anti-mitochondrial autoantibodies, and intrahepatic cytokine production. Disease expressions in the IFN-γ KO-dnTGFβRII mice, including liver immunopathology, were similar to those of dnTGFβRII mice, whereas the IL-12p40 KO-dnTGFβRII mice had a dramatic reduction in histological autoimmune cholangitis and significant decreases in levels of intrahepatic proinflammatory cytokines, but similar levels of AMA compared to dnTGFβRII controls. In conclusion, these data indicate that in this mouse model of PBC, signaling via the IL-12p40 is an essential requirement for development of autoimmune cholangitis. The results of these studies will play an important role in identifying pathways and reagents that will selectively inhibit IL-12 signaling for the outlining of future therapeutic strategies for human PBC.
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Deletion of Interleukin‐12p40 suppresses autoimmune cholangitis in dominant negative transforming growth factor β receptor type II mice
Hepatology, 2009Co-Authors: Katsunori Yoshida, Guo-xiang Yang, Weici Zhang, Masanobu Tsuda, Koichi Tsuneyama, Yuki Moritoki, Aftab A. Ansari, Kazuichi Okazaki, Zhe-xiong Lian, Ross L. CoppelAbstract:Our laboratory has reported that mice that express a dominant negative form of transforming growth factor-β receptor restricted to T cells (dnTGFβRII) develop an inflammatory biliary ductular disease with raised serum levels of IL-12p40 and other proinflammatory cytokines and anti-mitochondrial autoantibodies (AMA), closely resembling human primary biliary cirrhosis (PBC). We have utilized this mouse model to address the potential mechanisms of immune modulation of the liver disease by creating two unique genetic strains, IL-12p40 KO-dnTGFβRII mice and IFN-γ KO-dnTGFβRII mice. The two colonies of genetically modified mice and, for purposes of controls the dnTGFβRII mice, were monitored for liver immunopathology, anti-mitochondrial autoantibodies, and intrahepatic cytokine production. Disease expressions in the IFN-γ KO-dnTGFβRII mice, including liver immunopathology, were similar to those of dnTGFβRII mice, whereas the IL-12p40 KO-dnTGFβRII mice had a dramatic reduction in histological autoimmune cholangitis and significant decreases in levels of intrahepatic proinflammatory cytokines, but similar levels of AMA compared to dnTGFβRII controls. In conclusion, these data indicate that in this mouse model of PBC, signaling via the IL-12p40 is an essential requirement for development of autoimmune cholangitis. The results of these studies will play an important role in identifying pathways and reagents that will selectively inhibit IL-12 signaling for the outlining of future therapeutic strategies for human PBC.
Ross L. Coppel - One of the best experts on this subject based on the ideXlab platform.
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deletion of Interleukin 12p40 suppresses autoimmune cholangitis in dominant negative transforming growth factor β receptor type ii mice
Hepatology, 2009Co-Authors: Katsunori Yoshida, Guo-xiang Yang, Weici Zhang, Masanobu Tsuda, Koichi Tsuneyama, Yuki Moritoki, Aftab A. Ansari, Kazuichi Okazaki, Zhe-xiong Lian, Ross L. CoppelAbstract:Our laboratory has reported that mice that express a dominant negative form of transforming growth factor-β receptor restricted to T cells (dnTGFβRII) develop an inflammatory biliary ductular disease with raised serum levels of IL-12p40 and other proinflammatory cytokines and anti-mitochondrial autoantibodies (AMA), closely resembling human primary biliary cirrhosis (PBC). We have utilized this mouse model to address the potential mechanisms of immune modulation of the liver disease by creating two unique genetic strains, IL-12p40 KO-dnTGFβRII mice and IFN-γ KO-dnTGFβRII mice. The two colonies of genetically modified mice and, for purposes of controls the dnTGFβRII mice, were monitored for liver immunopathology, anti-mitochondrial autoantibodies, and intrahepatic cytokine production. Disease expressions in the IFN-γ KO-dnTGFβRII mice, including liver immunopathology, were similar to those of dnTGFβRII mice, whereas the IL-12p40 KO-dnTGFβRII mice had a dramatic reduction in histological autoimmune cholangitis and significant decreases in levels of intrahepatic proinflammatory cytokines, but similar levels of AMA compared to dnTGFβRII controls. In conclusion, these data indicate that in this mouse model of PBC, signaling via the IL-12p40 is an essential requirement for development of autoimmune cholangitis. The results of these studies will play an important role in identifying pathways and reagents that will selectively inhibit IL-12 signaling for the outlining of future therapeutic strategies for human PBC.
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Deletion of Interleukin‐12p40 suppresses autoimmune cholangitis in dominant negative transforming growth factor β receptor type II mice
Hepatology, 2009Co-Authors: Katsunori Yoshida, Guo-xiang Yang, Weici Zhang, Masanobu Tsuda, Koichi Tsuneyama, Yuki Moritoki, Aftab A. Ansari, Kazuichi Okazaki, Zhe-xiong Lian, Ross L. CoppelAbstract:Our laboratory has reported that mice that express a dominant negative form of transforming growth factor-β receptor restricted to T cells (dnTGFβRII) develop an inflammatory biliary ductular disease with raised serum levels of IL-12p40 and other proinflammatory cytokines and anti-mitochondrial autoantibodies (AMA), closely resembling human primary biliary cirrhosis (PBC). We have utilized this mouse model to address the potential mechanisms of immune modulation of the liver disease by creating two unique genetic strains, IL-12p40 KO-dnTGFβRII mice and IFN-γ KO-dnTGFβRII mice. The two colonies of genetically modified mice and, for purposes of controls the dnTGFβRII mice, were monitored for liver immunopathology, anti-mitochondrial autoantibodies, and intrahepatic cytokine production. Disease expressions in the IFN-γ KO-dnTGFβRII mice, including liver immunopathology, were similar to those of dnTGFβRII mice, whereas the IL-12p40 KO-dnTGFβRII mice had a dramatic reduction in histological autoimmune cholangitis and significant decreases in levels of intrahepatic proinflammatory cytokines, but similar levels of AMA compared to dnTGFβRII controls. In conclusion, these data indicate that in this mouse model of PBC, signaling via the IL-12p40 is an essential requirement for development of autoimmune cholangitis. The results of these studies will play an important role in identifying pathways and reagents that will selectively inhibit IL-12 signaling for the outlining of future therapeutic strategies for human PBC.