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TBX21-1993T/C polymorphism association with Th1 and Th17 response at periapex and with periapical lesions development risk.
Colavite, Priscila Maria; Cavalla, Franco; Garlet, Thiago Pompermaier; Azevedo, Michelle de Campos Soriani; Melchiades, Jessica Lima; Campanelli, Ana Paula; Letra, Ariadne; Trombone, Ana Paula Favaro; Silva, Renato Menezes; Garlet, Gustavo Pompermaier.
Afiliação
  • Colavite PM; Department of Biological Sciences, School of Dentistry of Bauru, University of Sao Paulo, Bauru, Brazil.
  • Cavalla F; Department of Biological Sciences, School of Dentistry of Bauru, University of Sao Paulo, Bauru, Brazil.
  • Garlet TP; Department of Conservative Dentistry, Faculty of Dentistry, University of Chile, Santiago, Chile.
  • Azevedo MCS; Department of Structural and Molecular Biology and Genetics, State University of Ponta Grossa, Ponta Grossa, Brazil.
  • Melchiades JL; Department of Biological Sciences, School of Dentistry of Bauru, University of Sao Paulo, Bauru, Brazil.
  • Campanelli AP; Department of Biological Sciences, School of Dentistry of Bauru, University of Sao Paulo, Bauru, Brazil.
  • Letra A; Department of Biological Sciences, School of Dentistry of Bauru, University of Sao Paulo, Bauru, Brazil.
  • Trombone APF; Department of Endodontics, School of Dentistry, University of Texas Health Science Center at Houston, Houston, Texas, USA.
  • Silva RM; Department of Diagnostic and Biomedical Sciences, and Center for Craniofacial Research, University of Texas Health Science Center at Houston, Houston, Texas, USA.
  • Garlet GP; Department of Biological and Health Sciences, Sagrado Coração University, Bauru, Brazil.
J Leukoc Biol ; 105(3): 609-619, 2019 03.
Article em En | MEDLINE | ID: mdl-30548981
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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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Doenças Periapicais / Células Th1 / Predisposição Genética para Doença / Proteínas com Domínio T / Polimorfismo de Nucleotídeo Único / Células Th17 Tipo de estudo: Etiology_studies / Risk_factors_studies Limite: Adolescent / Adult / Female / Humans / Male / Middle aged Idioma: En Revista: J Leukoc Biol Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Brasil País de publicação: Reino Unido

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Doenças Periapicais / Células Th1 / Predisposição Genética para Doença / Proteínas com Domínio T / Polimorfismo de Nucleotídeo Único / Células Th17 Tipo de estudo: Etiology_studies / Risk_factors_studies Limite: Adolescent / Adult / Female / Humans / Male / Middle aged Idioma: En Revista: J Leukoc Biol Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Brasil País de publicação: Reino Unido