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

P. M. Colavite,F. Cavalla,T. P. Garlet,M. Azevedo,J. L. Melchiades,A. Campanelli,A. Letra,A. Trombone,R. Silva,G. Garlet

Published 2018 in Journal of Leukocyte Biology

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.

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