THE ROLE OF IL-29 AND IL-28B IN THE INNATE IMMUNE RESPONSE Public Deposited

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  • March 22, 2019
Creator
  • Williamson, Megumi
    • Affiliation: School of Dentistry, Department of Periodontology
Abstract
  • Aims: Chronic periodontitis (CP) is an inflammatory disease induced by dysbiotic biofilm in a susceptible host, resulting in progressive attachment loss, and subsequent alveolar bone loss. Recent genome-wide association studies (GWAS) and genome-wide gene centric analysis on periodontal complex traits (PCTs) identified possible associations of IL-29 and IL-28B with periodontal diseases. However, the underlying mechanisms for how these genes contribute to the pathogenesis of periodontitis are largely unknown. The aims of the present study were to explore the role of IL-29 and IL-28B and their gene polymorphisms in the innate immune response by dendritic cells. Materials and methods: To explore the effect of IL-29 on the cytokine production in response to TLR4 stimulation, the IL-29 gene was knocked-down in THP-1 cells using IL-29 shRNA lentiviral particles. Pro- and anti-inflammatory cytokine levels were measured with Luminex® multiplex assay. To assess the effect of genetic variations in IL-29 and IL-28B, whole blood samples from fifteen subjects (6 subjects with major allele for both IL-29 and IL-28B, 5 subjects for major allele in IL-29 and minor allele in IL-28B, and 4 subjects with minor alleles for both genes) were collected and CD14+/CD16lo PBMCs were isolated to generate DCs. The effect of IL-29 and IL-28B SNPs on TNF-α and IL-10 expression in PBMC-derived dendritic cells were examined in response to stimulation with ligands of TLR1-2, TLR-2, and TLR4 using Luminex multiplex assay. Results: THP-1 cell-derived DCs showed decreased expression of TNF-α and IL-10 in IL-29 gene knockdown DCs, compared to DCs transduced with the scramble shRNA control lentiviral clone. IL-28B expression was decreased in IL-29 knockdown clones, while there was no difference between the scramble and two IL-29 gene knocked-down clones. Based on the evaluated samples, SNPs in IL-29 and IL-28B did not affect the expression levels of IL-10 or TNF-α in PBMC-derived DCs in response to TLR1-2, TLR2, and TLR4 stimulation. Similarly, the expression levels of IL-28A and IL-28B were unaffected by these SNPs. Conclusion: While the studied SNPs did not show effect on the evaluated cytokines, our results indicate that IL-29 and IL-28B may regulate pro- and anti-inflammatory cytokine production in DCs in an autocrine manner.
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Advisor
  • Marchesan, Julie
  • Amelio, Antonio
  • Morelli, Thiago
  • Offenbacher, Steven
Degree
  • Master of Science
Degree granting institution
  • University of North Carolina at Chapel Hill Graduate School
Graduation year
  • 2018
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