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Kathrin Suttner - One of the best experts on this subject based on the ideXlab platform.
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TBX21 and HLX1 Polymorphisms Influence Cytokine Secretion at Birth
PloS one, 2012Co-Authors: Vera Isabel Casaca, Kathrin Suttner, Sabina Illi, Isolde Schleich, Nikolaus Ballenberger, Elizabeth Klucker, Elif Turan, Erika Von Mutius, Michael Kabesch, Bianca SchaubAbstract:BACKGROUND TBX21 (T cell specific T-box transcription factor) and HLX1 (H.20-like homeobox 1) are crucial transcription factors of T(H)1-cells, inducing their differentiation and suppressing T(H)2 commitment, particularly important for early life immune development. This study investigated the influence of TBX21 and HLX1 single nucleotide polymorphisms (SNPs), which have previously been shown to be associated with asthma, on T(H)1/T(H)2 lineage cytokines at birth. METHODS AND FINDINGS Cord blood mononuclear cells (CBMCs) of 200 neonates were genotyped for two TBX21 and three HLX1 SNPs. CBMCs were stimulated with innate (Lipid A, LpA; Peptidoglycan, Ppg), adaptive stimuli (house dust mite Dermatophagoides pteronyssinus 1, Derp1) or mitogen (phytohemagglutinin, PHA). Cytokines, T-cells and mRNA expression of T(H)1/T(H)2-related genes were assessed. Atopic diseases during the first 3 years of life were assessed by questionnaire answered by the parents. Carriers of TBX21 promoter SNP rs17250932 and HLX1 promoter SNP rs2738751 showed reduced or trendwise reduced (p≤0.07) IL-5, IL-13 and TNF-α secretion after LpA-stimulation. Carriers of HLX1 SNP rs2738751 had lower IL-13 levels following Ppg-stimulation (p = 0.08). Carriers of HLX1 exon 1 SNP rs12141189 showed increased IL-5 (LpA, p = 0.007; Ppg, p = 0.10), trendwise increased IL-13 (LpA), higher GM-CSF (LpA/Ppg, p≤0.05) and trendwise decreased IFN-γ secretion (Derp1+LpA-stimulation, p = 0.1). Homozygous carriers of HLX1 promoter SNP rs3806325 showed increased IL-13 and IL-6 (unstimulated, p≤0.03). In carriers of TBX21 intron 3 SNP rs11079788 no differences in cytokine secretion were observed. mRNA expression of T(H)1/T(H)2-related genes partly correlated with cytokines at protein level. TBX21 SNP rs11079788 carriers developed less symptoms of atopic dermatitis at 3 years of age (p = 0.03). CONCLUSIONS Polymorphisms in TBX21 and HLX1 influenced primarily IL-5 and IL-13 secretion after LpA-stimulation in cord blood suggesting that genetic variations in the transcription factors essential for the T(H)1-pathway may contribute to modified T(H)2-immune responses already early in life. Further follow-up of the cohort is required to study the polymorphisms' relevance for immune-mediated diseases such as childhood asthma.
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polymorphismen in den transkriptionsfaktoren TBX21 hlx1 und gata3
2010Co-Authors: Kathrin SuttnerAbstract:Die Entstehung von Asthma bronchiale scheint mit einem Ungleichgewicht der T-Helferzellen zu Gunsten der Th2-Zellen assoziiert zu sein. Die wichtigsten Regulatoren der T-Zell-Pragung sind die Transkriptionsfaktoren TBX21, HLX1 und GATA3. Ziel der Studie war es daher, Polymorphismen (SNPs) in diesen Genen zu detektieren und ihre funktionelle Rolle bei Asthma bronchiale zu charakterisieren. Assoziationsstudien demonstrierten, dass SNPs in TBX21 und HLX1 das kindliche Asthmarisiko vor allem in Kombination signifikant beeinflussen, wahrend fur GATA3 keine Assoziationen beobachtet wurden. Funktionelle Studien zeigten, dass TBX21 und HLX1 Promotor-SNPs die Genexpression signifikant modifizieren und HLX1 SNPs das Bindeverhalten von SP- Transkriptionsfaktoren an den HLX1 Promotor verandern. Zudem wurde eine Protein-Protein Interaktion zwischen TBX21 und HLX1 detektiert. SNP- bedingte Aminosaureanderungen in TBX21 und HLX1 scheinen dieses Bindungsverhalten allerdings nicht zu beeinflussen.
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charakterisierung von genetischen varianten in den immunregulatorischen transkriptionsfaktoren TBX21 hlx1 und gata3 und deren funktionelle rolle bei der entstehung von asthma bronchiale
2010Co-Authors: Kathrin SuttnerAbstract:Die Entstehung von Asthma bronchiale scheint mit einem Ungleichgewicht der T-Helferzellen zu Gunsten der Th2-Zellen assoziiert zu sein. Die wichtigsten Regulatoren der T-Zell-Pragung sind die Transkriptionsfaktoren TBX21, HLX1 und GATA3. Ziel der Studie war es daher, Polymorphismen (SNPs) in diesen Genen zu detektieren und ihre funktionelle Rolle bei Asthma bronchiale zu charakterisieren. Assoziationsstudien demonstrierten, dass SNPs in TBX21 und HLX1 das kindliche Asthmarisiko vor allem in Kombination signifikant beeinflussen, wahrend fur GATA3 keine Assoziationen beobachtet wurden. Funktionelle Studien zeigten, dass TBX21 und HLX1 Promotor-SNPs die Genexpression signifikant modifizieren und HLX1 SNPs das Bindeverhalten von SP-Transkriptionsfaktoren an den HLX1 Promotor verandern. Zudem wurde eine Protein-Protein Interaktion zwischen TBX21 und HLX1 detektiert. SNP-bedingte Aminosaureanderungen in TBX21 und HLX1 scheinen dieses Bindungsverhalten allerdings nicht zu beeinflussen.
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TBX21 gene variants increase childhood asthma risk in combination with HLX1 variants
The Journal of allergy and clinical immunology, 2009Co-Authors: Kathrin Suttner, Philip Rosenstiel, Martin Depner, Michaela Schedel, Leonardo Araújo Pinto, Andreas Ruether, Jerzy Adamski, Norman Klopp, Thomas Illig, Christian VogelbergAbstract:Background The T cell–specific T-box transcription factor (TBX21) plays a crucial role in the regulation of the immune system because this factor induces the differentiation of T H 1 and blocks T H 2 commitment together with the homeobox transcription factor HLX1. Objective The role of genetic variants in TBX21 alone and in combination with HLX1 polymorphisms was investigated in the development of T H 2-associated atopy and asthma. Methods The TBX21 gene was resequenced in 37 adult volunteers. Polymorphisms identified were genotyped in a cross-sectional (N = 3099) and nested asthma case-control population (N = 1872) using mainly matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Effects of promoter polymorphisms on TBX21 gene expression were studied by reporter gene assays. Furthermore, the impact of combinations of TBX21 and HLX1 polymorphisms on the development of asthma was assessed by using a risk score model. Statistical analyses were performed by using SAS/Genetics. Results Forty-three polymorphisms were identified in the TBX21 gene. Considering a minor allele frequency of at least 10%, single nucleotide polymorphisms were assigned to 7 linkage disequilibrium blocks. Three tagging single nucleotide polymorphisms increased childhood asthma risk significantly (odds ratio [OR], 2.60, 95% CI, 1.34-5.03, P = .003; OR, 1.39, 95% CI, 1.02-1.90, P = .039; and OR, 1.97, 95% CI, 1.18-3.30, P = .009). TBX21 promoter polymorphisms contained in 2 blocks significantly influenced TBX21 promoter activity. In a risk score model, the combination of TBX21 and HLX1 polymorphisms increased the asthma risk by more than 3-fold. Conclusions These data suggest that TBX21 polymorphisms contribute to the development of asthma, potentially by altering TBX21 promoter activity. A risk score model indicates that TBX21 and HLX1 polymorphisms may have synergistic effects on asthma risk.
Song Chen - One of the best experts on this subject based on the ideXlab platform.
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Influence of TBX21 T-1993C variant on autoimmune hepatitis development by Yin-Yang 1 binding
World journal of gastroenterology, 2017Co-Authors: Wei Sun, Song ChenAbstract:Influence of TBX21 T-1993C variant on autoimmune hepatitis development by Yin-Yang 1 binding
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The role of upstream stimulatory factor 1 in the transcriptional regulation of the human TBX21 promoter mediated by the T-1514C polymorphism associated with systemic lupus erythematosus.
Immunogenetics, 2012Co-Authors: Yi You, Song ChenAbstract:T-bet is a key regulator for the lineage commitment in CD4+ T helper (Th) 1 cells by activating the hallmark production of interferon-γ. Previously, two single nucleotide polymorphisms (SNPs) in the TBX21 promoter, T-1993C and T-1514C, have been shown by statistic studies to associate with systemic lupus erythematosus (SLE). The effect of −1993 SNP on the Yin Yang 1 transcription factor-mediated promoter activity has been already indicated. This study aimed to investigate roles of the T-1514C SNP on TBX21 transcription and its functional effect by luciferase reporter, electrophoretic mobility shift assay (EMSA), chromatin immunoprecipitation (ChIP) assay, and flow cytometric analysis of intracellular T-bet, IFN-γ, and IL-4 expression in activated CD4+ T cells. The TBX21 promoter carrying −1514C possessed significantly lower transcriptional activity than that of −1514T and was markedly downregulated by the overexpression of upstream stimulatory factor 1 (USF-1) when compared with the promoter carrying −1514T. EMSA indicated that the transcription factor USF-1 was bound to the −1514C allele probe with the affinity higher than that to the −1514T allele probe. ChIP assay suggested that USF-1 bound around −1514 of TBX21 genomic DNA in vivo in the human T cell line Jurkat with −1514C/T. The individuals carrying −1514C allele were determined to have significantly diminished expression of T-bet and IFN-γ and increased IL-4 production in CD4+ T cells compared with those of −1514T allele. The findings demonstrate that the T-1514C polymorphism affects TBX21 gene expression and Th1 cytokine production by binding USF-1 to the SNP site.
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a common promoter variant of TBX21 is associated with allele specific binding to yin yang 1 and reduced gene expression
Scandinavian Journal of Immunology, 2011Co-Authors: Guohong Deng, Wei Zhao, Yunjie Dan, Yuming Wang, Song ChenAbstract:T-bet is a key regulator for the lineage commitment in CD4 T helper (Th) 1 cells by activating the hallmark production of interferon-γ, and its expression level is linked to autoimmune, infectious, and allergic diseases. A T to C base substitution has been identified at position -1993 in the TBX21 (encoding T-bet) promoter and has been associated with asthma and systemic lupus erythematosus. This study aimed to investigate the molecular mechanisms responsible for the influence of the T-1993C polymorphism on transcription and its functional effect by luciferase reporter, EMSAs, Chromatin immunoprecipitation assay, and flow cytometric analysis of intracellular T-bet, IFN-γ and IL-4 expression in activated CD4+ T cells. The presence of a -1993T allele obviously increases promoter activity compared with that of a promoter with a -1993C allele. TBX21 promoter carrying -1993C allele possesses significantly stronger binding affinity to the Yin Yang 1 (YY1) transcription factor than that carrying -1993T allele. YY1 overexpression decreased TBX21 promoter function in a T cell line, demonstrating that this element functions as a repressor. The C to T base exchange relieves the repression mediated by YY1. The individuals carrying -1993C allele were determined to have significantly diminished expression of TBX21 and IFN-γ and increased IL-4 production in cells compared with the individuals carrying -1993T allele (P < 0.05). These findings demonstrate that the TBX21 T-1993C polymorphism represses TBX21 expression and Th1 cytokine production through control of YY1, which might result in the imbalance between Th1 and Th2 immune responses in autoimmune or allergic diseases.
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A Common Promoter Variant of TBX21 is Associated with Allele Specific Binding to Yin‐Yang 1 and Reduced Gene Expression
Scandinavian journal of immunology, 2011Co-Authors: Guohong Deng, Wei Zhao, Yunjie Dan, Yuming Wang, Song ChenAbstract:T-bet is a key regulator for the lineage commitment in CD4 T helper (Th) 1 cells by activating the hallmark production of interferon-γ, and its expression level is linked to autoimmune, infectious, and allergic diseases. A T to C base substitution has been identified at position -1993 in the TBX21 (encoding T-bet) promoter and has been associated with asthma and systemic lupus erythematosus. This study aimed to investigate the molecular mechanisms responsible for the influence of the T-1993C polymorphism on transcription and its functional effect by luciferase reporter, EMSAs, Chromatin immunoprecipitation assay, and flow cytometric analysis of intracellular T-bet, IFN-γ and IL-4 expression in activated CD4+ T cells. The presence of a -1993T allele obviously increases promoter activity compared with that of a promoter with a -1993C allele. TBX21 promoter carrying -1993C allele possesses significantly stronger binding affinity to the Yin Yang 1 (YY1) transcription factor than that carrying -1993T allele. YY1 overexpression decreased TBX21 promoter function in a T cell line, demonstrating that this element functions as a repressor. The C to T base exchange relieves the repression mediated by YY1. The individuals carrying -1993C allele were determined to have significantly diminished expression of TBX21 and IFN-γ and increased IL-4 production in cells compared with the individuals carrying -1993T allele (P
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Association of TBX21 T-1993C polymorphism with viral persistence but not disease progression in hepatitis B virus carriers.
Hepatology research : the official journal of the Japan Society of Hepatology, 2009Co-Authors: Song Chen, Yunjie Dan, Yuming Wang, Wenli Zhao, Wenting Tan, Qing Mao, Xuemei Kuang, Guohong DengAbstract:Aim: Transcription factor T-bet is responsible for the differentiation of naive T lymphocytes, and its expression level is linked with different responses to some viral infections, including hepatitis B virus (HBV) infection. In this report we examine whether promoter polymorphisms of the TBX21 gene (encoding T-bet) are associated with susceptibility to HBV persistence or disease progression in chronic HBV carriers. Methods: Three previously reported promoter polymorphisms, T-1993C, T-1514C and G-1499A, were analyzed by polymerase chain reaction restriction fragment length polymorphism analysis. Two common polymorphisms, T-1993C and T-1514C, were selected for genotyping in 1074 chronic HBV carriers, 310 spontaneously recovered controls and 374 HBV naive controls. Of 1074 HBV carriers, 234 were considered to be asymptomatic carriers and 840 were found to have chronic progressive liver disease including cirrhosis and hepatocellular carcinoma. Haplotypes were constructed for each subject and associations with the susceptibility to persistent HBV infection were estimated by logistic regression. Results: The –1993C allele in the TBX21 promoter was significantly more common among chronic HBV carriers compared with recovered controls (χ2 = 6.65, P = 0.01). In contrast, the frequency of TT haplotype at positions –1993/–1514, was significantly higher in recovered controls than chronic HBV carriers (P = 0.0027, odds ratio = 1.57; 95% confidence interval, 1.16–2.12). In HBV carriers, the TBX21 promoter polymorphisms were not linked to disease progression. Conclusion: The TBX21 promoter polymorphisms do not appear to be determinant of disease progression in Chinese HBV carriers. The T-1993C polymorphism in the TBX21 promoter influences susceptibility to persistent HBV infection.
Luhua Wang - One of the best experts on this subject based on the ideXlab platform.
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TBX21 predicts prognosis of patients and drives cancer stem cell maintenance via the TBX21–IL-4 pathway in lung adenocarcinoma
Stem cell research & therapy, 2018Co-Authors: Shuangtao Zhao, Wenzhi Shen, Luhua WangAbstract:The Th1 cell-specific transcription factor TBX21 functions as a regulator of expression of a Th1 cytokine, interferon gamma (IFN-γ). However, the specific function of TBX21 correlated with cancer stemness remains unclear. Using univariate and multivariate survival analysis, TBX21was identified as an independent predictive factor and was associated with poor prognosis in 1389 patients with lung adenocarcinoma (LUAD). Its mechanism in the prognosis was explored by functional enrichment analysis and validated in bioexperiments. In the training and test sets, TBX21 could classify 1389 LUAD patients into high and low-risk groups with significantly different prognosis (P < 0.01). Its prognostic power was independent of other clinical factors including stage, age, gender and smoking status. Functional studies indicated that downregulating TBX21 in lung cancer cells decreased the fraction of cancer stem cells and their sphere and tumor initiation frequency. Furthermore, the study showed that TBX21 activation transduced a TBX21–IL-4 signaling cascade to promote tumor initiation, tumor growth and expression of stemness markers. These data demonstrated a key role of TBX21 in the maintenance of cancer stemness and that the TBX21–IL-4 pathway is a crucial factor contributing to lung carcinogenesis. TBX21 prognostic model correlated with cancer stemness via TBX21-IL-4 pathway in LUAD patients
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TBX21 predicts prognosis of patients and drives cancer stem cell maintenance via the TBX21 il 4 pathway in lung adenocarcinoma
Stem Cell Research & Therapy, 2018Co-Authors: Shuangtao Zhao, Wenzhi Shen, Luhua WangAbstract:The Th1 cell-specific transcription factor TBX21 functions as a regulator of expression of a Th1 cytokine, interferon gamma (IFN-γ). However, the specific function of TBX21 correlated with cancer stemness remains unclear. Using univariate and multivariate survival analysis, TBX21was identified as an independent predictive factor and was associated with poor prognosis in 1389 patients with lung adenocarcinoma (LUAD). Its mechanism in the prognosis was explored by functional enrichment analysis and validated in bioexperiments. In the training and test sets, TBX21 could classify 1389 LUAD patients into high and low-risk groups with significantly different prognosis (P < 0.01). Its prognostic power was independent of other clinical factors including stage, age, gender and smoking status. Functional studies indicated that downregulating TBX21 in lung cancer cells decreased the fraction of cancer stem cells and their sphere and tumor initiation frequency. Furthermore, the study showed that TBX21 activation transduced a TBX21–IL-4 signaling cascade to promote tumor initiation, tumor growth and expression of stemness markers. These data demonstrated a key role of TBX21 in the maintenance of cancer stemness and that the TBX21–IL-4 pathway is a crucial factor contributing to lung carcinogenesis. TBX21 prognostic model correlated with cancer stemness via TBX21-IL-4 pathway in LUAD patients
Gustavo Pompermaier Garlet - One of the best experts on this subject based on the ideXlab platform.
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TBX21‐1993T/C polymorphism association with Th1 and Th17 response at periapex and with periapical lesions development risk
Journal of leukocyte biology, 2018Co-Authors: Priscila Maria Colavite, Franco Cavalla, Thiago Pompermaier Garlet, Michelle De Campos Soriani Azevedo, Jessica Lima Melchiades, Ana Paula Campanelli, Ariadne Letra, Ana Paula Favaro Trombone, Renato Menezes Silva, Gustavo Pompermaier GarletAbstract:TBX21-1993T/C (rs4794067) polymorphism increases the transcriptional activity of the TBX21, essential for interferon gamma (IFNg) transcription, but its functional impact on development Th1- response in vivo remains unclear, as well its potential influence over inflammatory osteolytic conditions, such as periapical lesions. Therefore, this study comprises a case-control and functional investigation of TBX21 genetic variations impact on Th1 response in vivo and in vitro, and its impact on periapical lesions risk and outcome, performed with a population of healthy controls (H; N = 283) and patients presenting periapical lesions (L; N = 188) or deep caries (DC; N = 152). TBX21-1993T/C genotyping demonstrated that the polymorphic allele C, as well TC/TC+CC genotypes, was significantly less frequent in the L patients compared to H and DC groups. Additionally, gene expression analysis demonstrates that T-cell-specific T-box transcription factor (Tbet) and IFNg transcripts levels were downregulated whereas IL-17 levels were upregulated in the TBX21-1993 C carriers (TC/TC+CC) in comparison with the TT group. Also, while TT and TC+CC genotypes are equally prevalent in the lesions presenting low IFN/IL17 ratio, a significant decrease in polymorphic TC+CC genotypes was observed in lesions presenting intermediate and high IFN/IL17 ratio. In vitro experiments confirmed the predisposition to Th1 polarization associated with TBX21-1993, since PBMC CD4 T cells from T allele carriers produce higher IFNg levels upon CD3/CD28 stimulation than the C group, in both standard/neutral and Th1-polarizing culture conditions. In conclusion, the TBX21-1993 T allele and TC/CC genotypes predispose to Th1-type immune response development in vitro, influence immune response polarization in vivo, and consequently account for the risk for apical periodontitis development.
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TBX21-1993T/C (rs4794067) polymorphism is associated with increased risk of chronic periodontitis and increased T-bet expression in periodontal lesions, but does not significantly impact the IFN-g transcriptional level or the pattern of periodontopha
Virulence, 2015Co-Authors: Franco Cavalla, Priscila Maria Colavite, Ariadne Letra, Ana Paula Favaro Trombone, Renato Menezes Silva, Claudia Cristina Biguetti, Elcia Varise Silveira, Walter Martins, Gustavo Pompermaier GarletAbstract:Th1-polarized host response, mediated by IFN-γ, has been associated with increased severity of periodontal disease as well as control of periodontal infection. The functional polymorphism TBX21-1993T/C (rs4794067) increases the transcriptional activity of the TBX21 gene (essential for Th1 polarization) resulting in a predisposition to a Th-1 biased immune response. Thus, we conducted a case-control study, including a population of healthy controls (H, n = 218), chronic periodontitis (CP, n = 197), and chronic gingivitis patients (CG, n = 193), to investigate if genetic variations in TBX21 could impact the development of Th1 responses, and consequently influence the pattern of bacterial infection and periodontitis outcome. We observed that the polymorphic allele T was significantly enriched in the CP patients compared to CG subjects, while the H controls demonstrated and intermediate genotype. Also, investigating the putative functionality TBX21-1993T/C in the modulation of local response, we observed that...
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TBX21 1993t c rs4794067 polymorphism is associated with increased risk of chronic periodontitis and increased t bet expression in periodontal lesions but does not significantly impact the ifn g transcriptional level or the pattern of periodontophatic
Virulence, 2015Co-Authors: Franco Cavalla, Priscila Maria Colavite, Ariadne Letra, Ana Paula Favaro Trombone, Renato Menezes Silva, Claudia Cristina Biguetti, Elcia Varise Silveira, Walter Martins, Gustavo Pompermaier GarletAbstract:Th1-polarized host response, mediated by IFN-γ, has been associated with increased severity of periodontal disease as well as control of periodontal infection. The functional polymorphism TBX21-1993T/C (rs4794067) increases the transcriptional activity of the TBX21 gene (essential for Th1 polarization) resulting in a predisposition to a Th-1 biased immune response. Thus, we conducted a case-control study, including a population of healthy controls (H, n = 218), chronic periodontitis (CP, n = 197), and chronic gingivitis patients (CG, n = 193), to investigate if genetic variations in TBX21 could impact the development of Th1 responses, and consequently influence the pattern of bacterial infection and periodontitis outcome. We observed that the polymorphic allele T was significantly enriched in the CP patients compared to CG subjects, while the H controls demonstrated and intermediate genotype. Also, investigating the putative functionality TBX21-1993T/C in the modulation of local response, we observed that...
Franco Cavalla - One of the best experts on this subject based on the ideXlab platform.
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TBX21 1993t c polymorphism association with th1 and th17 response at periapex and with periapical lesions development risk
Journal of Leukocyte Biology, 2019Co-Authors: Priscila Maria Colavite, Franco Cavalla, Thiago Pompermaier Garlet, Michelle De Campos Soriani Azevedo, Jessica Lima Melchiades, Ana Paula Campanelli, Ariadne Letra, Ana Paula Favaro Trombone, Renato Menezes SilvaAbstract:TBX21-1993T/C (rs4794067) polymorphism increases the transcriptional activity of the TBX21, essential for interferon gamma (IFNg) transcription, but its functional impact on development Th1- response in vivo remains unclear, as well its potential influence over inflammatory osteolytic conditions, such as periapical lesions. Therefore, this study comprises a case-control and functional investigation of TBX21 genetic variations impact on Th1 response in vivo and in vitro, and its impact on periapical lesions risk and outcome, performed with a population of healthy controls (H; N = 283) and patients presenting periapical lesions (L; N = 188) or deep caries (DC; N = 152). TBX21-1993T/C genotyping demonstrated that the polymorphic allele C, as well TC/TC+CC genotypes, was significantly less frequent in the L patients compared to H and DC groups. Additionally, gene expression analysis demonstrates that T-cell-specific T-box transcription factor (Tbet) and IFNg transcripts levels were downregulated whereas IL-17 levels were upregulated in the TBX21-1993 C carriers (TC/TC+CC) in comparison with the TT group. Also, while TT and TC+CC genotypes are equally prevalent in the lesions presenting low IFN/IL17 ratio, a significant decrease in polymorphic TC+CC genotypes was observed in lesions presenting intermediate and high IFN/IL17 ratio. In vitro experiments confirmed the predisposition to Th1 polarization associated with TBX21-1993, since PBMC CD4 T cells from T allele carriers produce higher IFNg levels upon CD3/CD28 stimulation than the C group, in both standard/neutral and Th1-polarizing culture conditions. In conclusion, the TBX21-1993 T allele and TC/CC genotypes predispose to Th1-type immune response development in vitro, influence immune response polarization in vivo, and consequently account for the risk for apical periodontitis development.
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TBX21‐1993T/C polymorphism association with Th1 and Th17 response at periapex and with periapical lesions development risk
Journal of leukocyte biology, 2018Co-Authors: Priscila Maria Colavite, Franco Cavalla, Thiago Pompermaier Garlet, Michelle De Campos Soriani Azevedo, Jessica Lima Melchiades, Ana Paula Campanelli, Ariadne Letra, Ana Paula Favaro Trombone, Renato Menezes Silva, Gustavo Pompermaier GarletAbstract:TBX21-1993T/C (rs4794067) polymorphism increases the transcriptional activity of the TBX21, essential for interferon gamma (IFNg) transcription, but its functional impact on development Th1- response in vivo remains unclear, as well its potential influence over inflammatory osteolytic conditions, such as periapical lesions. Therefore, this study comprises a case-control and functional investigation of TBX21 genetic variations impact on Th1 response in vivo and in vitro, and its impact on periapical lesions risk and outcome, performed with a population of healthy controls (H; N = 283) and patients presenting periapical lesions (L; N = 188) or deep caries (DC; N = 152). TBX21-1993T/C genotyping demonstrated that the polymorphic allele C, as well TC/TC+CC genotypes, was significantly less frequent in the L patients compared to H and DC groups. Additionally, gene expression analysis demonstrates that T-cell-specific T-box transcription factor (Tbet) and IFNg transcripts levels were downregulated whereas IL-17 levels were upregulated in the TBX21-1993 C carriers (TC/TC+CC) in comparison with the TT group. Also, while TT and TC+CC genotypes are equally prevalent in the lesions presenting low IFN/IL17 ratio, a significant decrease in polymorphic TC+CC genotypes was observed in lesions presenting intermediate and high IFN/IL17 ratio. In vitro experiments confirmed the predisposition to Th1 polarization associated with TBX21-1993, since PBMC CD4 T cells from T allele carriers produce higher IFNg levels upon CD3/CD28 stimulation than the C group, in both standard/neutral and Th1-polarizing culture conditions. In conclusion, the TBX21-1993 T allele and TC/CC genotypes predispose to Th1-type immune response development in vitro, influence immune response polarization in vivo, and consequently account for the risk for apical periodontitis development.
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TBX21-1993T/C (rs4794067) polymorphism is associated with increased risk of chronic periodontitis and increased T-bet expression in periodontal lesions, but does not significantly impact the IFN-g transcriptional level or the pattern of periodontopha
Virulence, 2015Co-Authors: Franco Cavalla, Priscila Maria Colavite, Ariadne Letra, Ana Paula Favaro Trombone, Renato Menezes Silva, Claudia Cristina Biguetti, Elcia Varise Silveira, Walter Martins, Gustavo Pompermaier GarletAbstract:Th1-polarized host response, mediated by IFN-γ, has been associated with increased severity of periodontal disease as well as control of periodontal infection. The functional polymorphism TBX21-1993T/C (rs4794067) increases the transcriptional activity of the TBX21 gene (essential for Th1 polarization) resulting in a predisposition to a Th-1 biased immune response. Thus, we conducted a case-control study, including a population of healthy controls (H, n = 218), chronic periodontitis (CP, n = 197), and chronic gingivitis patients (CG, n = 193), to investigate if genetic variations in TBX21 could impact the development of Th1 responses, and consequently influence the pattern of bacterial infection and periodontitis outcome. We observed that the polymorphic allele T was significantly enriched in the CP patients compared to CG subjects, while the H controls demonstrated and intermediate genotype. Also, investigating the putative functionality TBX21-1993T/C in the modulation of local response, we observed that...
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TBX21 1993t c rs4794067 polymorphism is associated with increased risk of chronic periodontitis and increased t bet expression in periodontal lesions but does not significantly impact the ifn g transcriptional level or the pattern of periodontophatic
Virulence, 2015Co-Authors: Franco Cavalla, Priscila Maria Colavite, Ariadne Letra, Ana Paula Favaro Trombone, Renato Menezes Silva, Claudia Cristina Biguetti, Elcia Varise Silveira, Walter Martins, Gustavo Pompermaier GarletAbstract:Th1-polarized host response, mediated by IFN-γ, has been associated with increased severity of periodontal disease as well as control of periodontal infection. The functional polymorphism TBX21-1993T/C (rs4794067) increases the transcriptional activity of the TBX21 gene (essential for Th1 polarization) resulting in a predisposition to a Th-1 biased immune response. Thus, we conducted a case-control study, including a population of healthy controls (H, n = 218), chronic periodontitis (CP, n = 197), and chronic gingivitis patients (CG, n = 193), to investigate if genetic variations in TBX21 could impact the development of Th1 responses, and consequently influence the pattern of bacterial infection and periodontitis outcome. We observed that the polymorphic allele T was significantly enriched in the CP patients compared to CG subjects, while the H controls demonstrated and intermediate genotype. Also, investigating the putative functionality TBX21-1993T/C in the modulation of local response, we observed that...
