TBX21-1993T/C polymorphism association with Th1 and Th17 response at periapex and with periapical lesions development risk

Author(s)

Colavite, Priscila Maria ^[1] ; Cavalla, Franco ^{[1, 2]} ; Garlet, Thiago Pompermaier ^[3] ; Soriani Azevedo, Michelle de Campos ^[1] ; Melchiades, Jessica Lima ^[1] ; Campanelli, Ana Paula ^[1] ; Letra, Ariadne ^{[4, 5, 6]} ; Favaro Trombone, Ana Paula ^[7] ; Silva, Renato Menezes ^[4] ; Garlet, Gustavo Pompermaier ^[1]

Affiliation

^[1] Univ Sao Paulo, Sch Dent Bauru, Dept Biol Sci, Al Octavio Pinheiro Brisola 9-75, BR-17012901 Bauru, SP - Brazil

^[2] Univ Chile, Dept Conservat Dent, Fac Dent, Santiago - Chile

^[3] Univ Estadual Ponta Grossa, Dept Struct & Mol Biol & Genet, Ponta Grossa - Brazil

^[4] Univ Texas Hlth Sci Ctr Houston, Sch Dent, Dept Endodont, Houston, TX 77030 - USA

^[5] Univ Texas Hlth Sci Ctr Houston, Dept Diagnost & Biomed Sci, Houston, TX 77030 - USA

^[6] Univ Texas Hlth Sci Ctr Houston, Ctr Craniofacial Res, Houston, TX 77030 - USA

^[7] Sagrado Coracao Univ, Dept Biol & Hlth Sci, Bauru - Brazil

• Document type: Journal article
• Source: Journal of Leukocyte Biology; v. 105, n. 3, p. 609-619, MAR 2019.
• Web of Science Citations: 1

Abstract

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. (AU)

• FAPESP's process: 14/03276-0 - Influence of genetic polymorphisms in the colonization/recolonization patterns in chronic periodontitis patients
• Grantee: Ian Franco Cavalla Ruiz
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 15/18163-9 - Potential common genetic susceptibility traits shared by chronic and apical periodontitis: focus on SNPs assessment followed by bioinformatics analysis including clinical, microbiological and inflammatory/immunological data
• Grantee: Ian Franco Cavalla Ruiz
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• FAPESP's process: 15/24637-3 - MSCs and m2 as determinants of the constructive or destructive nature of inflammatory microenvironments associated with bone tissue
• Grantee: Gustavo Pompermaier Garlet
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 14/17886-4 - Influence of genetic polymorphisms in the patterns of bacterial colonization and recolonization in chornic periodontitis patients
• Grantee: Gustavo Pompermaier Garlet
• Support Opportunities: Regular Research Grants