Functional Haplotypes in Interleukin 4 Gene Associated with Periodontitis

• Published in: PloS one Vol. 12; no. 1; p. e0169870
• Main Authors: Anovazzi, Giovana, Medeiros, Marcell Costa de, Pigossi, Suzane Cristina, Finoti, Livia Sertori, Mayer, Marcia Pinto Alves, Rossa, Carlos, Scarel-Caminaga, Raquel Mantuaneli
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 23.01.2017; Public Library of Science (PLoS)
• Subjects: Aggregatibacter actinomycetemcomitans; Bacteria; Biology and Life Sciences; Chronic Disease; Comparative analysis; Cytokines; Cytokines - biosynthesis; Cytokines - blood; Cytokines - genetics; Dental plaque; Dental research; Dentistry; Development and progression; Disease; Disease susceptibility; Ethics; Gene Expression; Genetic aspects; Genetic diversity; Genotype & phenotype; Genotypes; Gum disease; Haplotypes; Humans; Immune response; Immune system; Immunology; Interleukin 4; Interleukin-4 - genetics; Lymphocytes T; Medicine and Health Sciences; Morphology; Periodontitis; Periodontitis - genetics; Periodontitis - microbiology; Peripheral blood; Physiological aspects; Porphyromonas gingivalis; Porphyromonas gingivalis - pathogenicity; Risk factors; Studies; Surgery; Teeth; Tumor necrosis factor-TNF; Brazil
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0169870

Chronic periodontitis (CP) is an infectious inflammatory disease that affects tooth-supporting structures and in which dental plaque bacteria, immune mechanisms and genetic predisposition play important roles. Interleukin 4 (IL-4) is a key anti-inflammatory cytokine with relevant action in imbalances in inflamed periodontal tissue. Individuals carrying the TCI/CCI genotype (S-haplotype) of the IL-4 gene are 5 times more susceptible to CP, whereas the CTI/TTD genotype (P-haplotype) confers protection against CP. Compared with the S-haplotype, subjects with the P-haplotype produce higher levels of the IL-4 protein after non-surgical periodontal therapy. The present in vitro study aimed to investigate the functionality of IL-4 haplotypes in immune cells to obtain insight into the influence of these genetic variations in regulating immune responses to CP-associated bacteria. Peripheral blood was collected from 6 subjects carrying each haplotype, and their immune cells were challenged with periodontopathogens to compare responses of the different haplotypes with regard to gene expression, protein secretion and the immunophenotype of T helper responses. We found higher IL-4 mRNA and protein levels in the P-haplotype, which also presented higher levels of anti-inflammatory cytokines. In contrast, cells from S-haplotype subjects responded with higher levels of pro-inflammatory cytokines. S-haplotype individuals exhibited significantly greater polarization toward the Th1 phenotype, whereas the P-haplotype was associated with an attenuated response to periodontopathogens, with suggestive skewing toward Th2/M2 phenotypes. In conclusion, IL-4 genetic variations associated with susceptibility to or protection against chronic periodontitis are directly associated with influencing the response of immune cells to periodontopathogens.