Last Modified

• June 7, 2019

Creator

• Sun, Lu
  • Affiliation: School of Dentistry, Oral and Craniofacial Biomedicine PhD Program

Abstract

• Periodontal disease is a polygenic disease that is associated with inflammatory response to the oral biofilm. Although it is believed that microbial pathogens are necessary to the causal pathway, a key factor to determine whether individuals will develop periodontitis is the way how the hosts respond to the microflora resides in their periodontium. Genetic polymorphisms that will cause a change in the encoded protein or its expression, which may alter host innate or adaptive immunity, such as host barrier function and inflammatory responses, to microorganism and determine susceptibility to inflammatory disease. Thus it is necessary to seek candidate genetic function to explain the differences in susceptibility to periodontal disease. Our recent genome-wide association study (GWAS) identified a missense single nucleotide polymorphism SNP (rs3099950) in the gene MORN2 that codes for a key membrane protein. We have also identified a missense SNP (rs13190932) in the gene TRAF3IP2 locus which is involved IL-17 signaling. These two genetic variants are associated with a P.gingivalis (P.g) dominant and A. actinomycetemcomitans (A.a) dominant periodontal disease subtypes. To date, only one study has described the function of MORN2 that serves as a macrophage protein that promotes the phagocytosis and killing of organisms via LC3-asscociated phagocytosis. TRAF3IP2 is involved in IL-17 signaling and mucosal immunity serving as an adaptor protein for the IL-17 receptor. However, the role of MORN2 and TRAF3IP2 in periodontal disease is unknown. In Chapter 1, the background of periodontal disease and how the SNPs were identified by GWAS were described. In Chapter 2, we investigated the role of MORN2 in modulating innate immune response to periodontal pathogens and our studies suggest that MORN2 plays a critical role in the LC3-associated phagocytosis – mediated killing of periodontal pathogen (P.g) as well as cytokine/chemokine response through Ca2+ flux and NF-kB activation. In Chapter 3, we explored the role of TRAF3IP2 mediated IL-17 pathway in periodontal disease. Our study suggests that TRAF3IP2 engaged homeostatic IL-17 pathway plays a protective role in a P.g induced alveolar bone loss and colonization through neutrophil recruitment, maintenance epithelial barrier and induction of antimicrobial peptides. Defective TRAF3IP2 shifts the oral commensal communities. Finally in Chapter 4, we discuss the significance and future study directions. In summary, these findings clarify the molecular mechanism of MORN2 and TRAF3IP2 function and provide insight into the genetic basis of MORN2 and TRAF3IP2 in periodontal disease susceptibility.

Date of publication

• May 2018

Keyword

• Dentistry

DOI

• https://doi.org/10.17615/g29x-ys72

Resource type

• Dissertation

Rights statement

• In Copyright

Advisor

• Bencharit, Sompop
• Yamauchi, Mitsuo
• Darville, Toni
• Offenbacher, Steven
• Webster-Cyriaque, Jennifer

Degree

• Doctor of Philosophy

Degree granting institution

• University of North Carolina at Chapel Hill Graduate School

Graduation year

• 2018

Language

• English

Parents:

This work has no parents.

Items

Thumbnail	Title	Date Uploaded	Visibility	Actions
	Sun_unc_0153D_17958.pdf	2019-04-11	Embargo	Press to Select an action Download
	PREMIS_Events_Metadata_0_b300d0b1-a7c5-4e2b-9d75-8c57bf4ce7c4.txt	2019-04-11	Public	Press to Select an action Download
	original_metadata_file_b300d0b1-a7c5-4e2b-9d75-8c57bf4ce7c4.xml	2019-04-11	Public	Press to Select an action Download