IL-22 is a novel cytokine in the IL-10 family that functions to promote innate immunity of tissues against infection. Although CD4＋ helper T lymphocytes （TH） were found as a source of IL-22, the regulation of this ...IL-22 is a novel cytokine in the IL-10 family that functions to promote innate immunity of tissues against infection. Although CD4＋ helper T lymphocytes （TH） were found as a source of IL-22, the regulation of this cytokine has been poorly understood. Here, we show that IL-22 is expressed at both mRNA and protein levels by a novel subset of TH cells that also makes IL-17. IL-22 and IL-17 were found to be coordinately regulated by TGFI3 and IL-6 during TH differentiation by real-time PCR as well as ELISA analysis. However, IL-22 does not regulate TH differentiation; exogenous IL-22 or an IL-22 antagonist had no effect on TH differentiation. These data demonstrate a novel cytokine expressed by IL-17-producing T cells, and suggest interaction and synergy of IL-22 and IL-l 7 signaling pathways in tissue inflammation and autoimmune diseases.展开更多
The genomic and cDNA sequences of the CD3γ/δ and CD3ε homologues in the mandarin fish, Siniperca chuatsi, were determined. As in other vertebrate CD3 molecules, the deduced amino acid sequences of mandarin fish CD3...The genomic and cDNA sequences of the CD3γ/δ and CD3ε homologues in the mandarin fish, Siniperca chuatsi, were determined. As in other vertebrate CD3 molecules, the deduced amino acid sequences of mandarin fish CD3γ/δ and CD3ε contained conserved residues and motifs, such as cysteine residues and CXXC and immunoreceptor tyrosine-based activation motifs. However, mandarin fish CD3γ/δ and CD3ε showed some differences to their mammalian counterparts, specifically the absence of a negatively charged residue in the transmembrane region of CD3γ/δ. Additionally, while an N-glycosylation site was present in CD3c, the site was not observed in CD3γ/δ. The CD3γ/δ and CD3ε subunit sequences contain six and five exons, respectively, consistent with homologues from Atlantic salmon, Salmo salar. Phylogenetic analysis also revealed that CD3γ/δ and CD3ε in mandarin fish are closely related to their counterparts in Acanthopterygian fish. Real-time PCR showed CD3γ/δ and CD3ε were expressed mainly in the thymus and spleen in normal healthy fish and, to a lesser extent, in mucosal-associated lymphoid tissues, such as the intestine and gills. When lymphocytes isolated from head kidney were treated with the mitogens phytohemagglutinin, concanavalin, and polyriboinosinic polyribocytidylic acid, mRNA expression levels of CD3γ/δ and CD3ε were significantly elevated within 12 h of treatment. This indicated the presence of T lymphocytes in the head kidney of teleost fish, and also the recognition of mitogens by the lymphocytes. Mandarin fish infected with the bacterial pathogen Flavobacterium columnare also showed an increase in the expression of CD3γ/δ and CD3ε mR_NA, indicating that CD3γ/δ and CD3ε lymphocytes are involved in the immune response of this species.展开更多
Autoimmune mechanisms, including cellular and humoral immune, are likely to participate in the pathogenesis of at least a subgroup of idiopathic dilated cardiomyopathy （IDC）, in which cellular immune-mediation plays...Autoimmune mechanisms, including cellular and humoral immune, are likely to participate in the pathogenesis of at least a subgroup of idiopathic dilated cardiomyopathy （IDC）, in which cellular immune-mediation plays a more important role. Cytotoxic T lymphocyte associated antigen-4 （CTLA-4） is the major negative regulatory factor of cellular immunity. This study was conducted to investigate the association of CTIA-4 gene exon 1 A49→G polymorphism with susceptibility to IDC in Han Chinese and its influences on serum soluble CTIA-4 （sCrLA-4） and Th1/Th2 cytokine bias. Polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） techniques were used to analyze the dimorphism of CTL4-4 exon 1 in the unrelated Han ethnic population in Heilongjiang Province （ including 48 IDC patients and 50 normal controls）. Serum sCTLA-4, IFN-γ and IL-4 were evaluated by ELISA, with the ratio of IFN-γ/IL-4 as indicator for Th1/Th2 bias. Compared with controls, the frequencies of GG genotype （0.6042 and 0.3600, P = 0.012） and the G allele （0.7396 and 0.5600, P = 0.008） were significantly increased in IDC patients. Increased serum sCTIA-4 was found in the 1DC group compared with the controls [ （ 1.87 ± 1.06） μg/L vs. （0.54 ± 0.19） 〉g/L, P 〈 0.05 ~. 1FN-7 was much lower in IDC patients than that of the controls [ （ 16.38 ± 6.25） ng/L vs. （29.81 ± 10.66） ng/L （P 〈 0.05）~., whereas no statistical difference of IL-4 was found between the two groups I （12.85 ± 1.86） ng/L vs. （12.11 ± 2.76） ng/L], so the ratio of IFN-γ/IL-4 declined significantly （ 1.63 ± 0.50 vs. 3.01 ± 0.89, P 〈 0.05）. Linear regression analysis manifested a significant interrelationship between the GG genotype, G allele frequencies and serum sCTLA-4, IFN-γ/IL-4 in the IDC group （ r = 0.57, P = 0. 021 and r = 0.32, P = 0. 036）. CTLA-4 gene A49→G substitution was associated with an increased IDC risk, which implicated that the CTLA-4 gene exon 1 may have a considerable role in autoimmune cardiac damage, possibly via a Thr→Ala change in signal peptide, which influences the protein synthesis and modification processes, with a result of functional alteration of sCTLA-4. The bias of Th1/Th2 paradigm was associated with the increased sCTIA-4 under certain background of immunogenetics.展开更多
文摘IL-22 is a novel cytokine in the IL-10 family that functions to promote innate immunity of tissues against infection. Although CD4＋ helper T lymphocytes （TH） were found as a source of IL-22, the regulation of this cytokine has been poorly understood. Here, we show that IL-22 is expressed at both mRNA and protein levels by a novel subset of TH cells that also makes IL-17. IL-22 and IL-17 were found to be coordinately regulated by TGFI3 and IL-6 during TH differentiation by real-time PCR as well as ELISA analysis. However, IL-22 does not regulate TH differentiation; exogenous IL-22 or an IL-22 antagonist had no effect on TH differentiation. These data demonstrate a novel cytokine expressed by IL-17-producing T cells, and suggest interaction and synergy of IL-22 and IL-l 7 signaling pathways in tissue inflammation and autoimmune diseases.
基金Supported by the National Natural Science Foundation of China (No.U0631010),the Government of Guangdong Provincethe National Basic Research Program of China (973 Program) (No. 2009CB118703)
文摘The genomic and cDNA sequences of the CD3γ/δ and CD3ε homologues in the mandarin fish, Siniperca chuatsi, were determined. As in other vertebrate CD3 molecules, the deduced amino acid sequences of mandarin fish CD3γ/δ and CD3ε contained conserved residues and motifs, such as cysteine residues and CXXC and immunoreceptor tyrosine-based activation motifs. However, mandarin fish CD3γ/δ and CD3ε showed some differences to their mammalian counterparts, specifically the absence of a negatively charged residue in the transmembrane region of CD3γ/δ. Additionally, while an N-glycosylation site was present in CD3c, the site was not observed in CD3γ/δ. The CD3γ/δ and CD3ε subunit sequences contain six and five exons, respectively, consistent with homologues from Atlantic salmon, Salmo salar. Phylogenetic analysis also revealed that CD3γ/δ and CD3ε in mandarin fish are closely related to their counterparts in Acanthopterygian fish. Real-time PCR showed CD3γ/δ and CD3ε were expressed mainly in the thymus and spleen in normal healthy fish and, to a lesser extent, in mucosal-associated lymphoid tissues, such as the intestine and gills. When lymphocytes isolated from head kidney were treated with the mitogens phytohemagglutinin, concanavalin, and polyriboinosinic polyribocytidylic acid, mRNA expression levels of CD3γ/δ and CD3ε were significantly elevated within 12 h of treatment. This indicated the presence of T lymphocytes in the head kidney of teleost fish, and also the recognition of mitogens by the lymphocytes. Mandarin fish infected with the bacterial pathogen Flavobacterium columnare also showed an increase in the expression of CD3γ/δ and CD3ε mR_NA, indicating that CD3γ/δ and CD3ε lymphocytes are involved in the immune response of this species.
文摘Autoimmune mechanisms, including cellular and humoral immune, are likely to participate in the pathogenesis of at least a subgroup of idiopathic dilated cardiomyopathy （IDC）, in which cellular immune-mediation plays a more important role. Cytotoxic T lymphocyte associated antigen-4 （CTLA-4） is the major negative regulatory factor of cellular immunity. This study was conducted to investigate the association of CTIA-4 gene exon 1 A49→G polymorphism with susceptibility to IDC in Han Chinese and its influences on serum soluble CTIA-4 （sCrLA-4） and Th1/Th2 cytokine bias. Polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） techniques were used to analyze the dimorphism of CTL4-4 exon 1 in the unrelated Han ethnic population in Heilongjiang Province （ including 48 IDC patients and 50 normal controls）. Serum sCTLA-4, IFN-γ and IL-4 were evaluated by ELISA, with the ratio of IFN-γ/IL-4 as indicator for Th1/Th2 bias. Compared with controls, the frequencies of GG genotype （0.6042 and 0.3600, P = 0.012） and the G allele （0.7396 and 0.5600, P = 0.008） were significantly increased in IDC patients. Increased serum sCTIA-4 was found in the 1DC group compared with the controls [ （ 1.87 ± 1.06） μg/L vs. （0.54 ± 0.19） 〉g/L, P 〈 0.05 ~. 1FN-7 was much lower in IDC patients than that of the controls [ （ 16.38 ± 6.25） ng/L vs. （29.81 ± 10.66） ng/L （P 〈 0.05）~., whereas no statistical difference of IL-4 was found between the two groups I （12.85 ± 1.86） ng/L vs. （12.11 ± 2.76） ng/L], so the ratio of IFN-γ/IL-4 declined significantly （ 1.63 ± 0.50 vs. 3.01 ± 0.89, P 〈 0.05）. Linear regression analysis manifested a significant interrelationship between the GG genotype, G allele frequencies and serum sCTLA-4, IFN-γ/IL-4 in the IDC group （ r = 0.57, P = 0. 021 and r = 0.32, P = 0. 036）. CTLA-4 gene A49→G substitution was associated with an increased IDC risk, which implicated that the CTLA-4 gene exon 1 may have a considerable role in autoimmune cardiac damage, possibly via a Thr→Ala change in signal peptide, which influences the protein synthesis and modification processes, with a result of functional alteration of sCTLA-4. The bias of Th1/Th2 paradigm was associated with the increased sCTIA-4 under certain background of immunogenetics.
