Samia, Filzah
(2024)
Insights from Sc-RNA Analysis: Immunomodulation and Neutrophils in Periodontitis.
Master's Thesis, University of Pittsburgh.
(Unpublished)
Abstract
This thesis explores the complex interplay of immunomodulation and neutrophil dynamics within the context of periodontal disease (PD), a chronic inflammatory condition characterized by the degradation of tooth-supporting tissues and microbial imbalance. Central to the pathogenesis of PD are the interactions between various components of the immune system, including innate and adaptive immune cells, cytokines, chemokines, and lipid mediators. Neutrophils are fundamental to the innate immune response in the periodontal environment, serving as the first responders to pathogenic challenges and the overseers of homeostasis. This thesis investigates the therapeutic potential of neutrophil modulation in PD through the local sustained delivery of the chemokine CCL2, encapsulated within biodegradable PLGA microspheres. Utilizing the established murine ligature-induced periodontitis model, this study provides a multifaceted assessment of periodontal health. Parameters such as bone integrity, gene expression profiles, neutrophil cluster dynamics, osteoclastic activity, and the structural organization of the periodontal ligament were evaluated to analyze the effectiveness of the intervention. Advanced single-cell RNA sequencing was employed to unravel the complex gene expression landscape of periodontal neutrophils, uncovering distinct phenotypic subsets and pathways that could potentially guide disease progression or therapeutic resolution. Furthermore, the thesis investigates the nuanced interplay between neutrophils and macrophages, revealing a complex network of interactions crucial for periodontal disease outcomes. By integrating these cellular and molecular insights, the thesis underscores the translational potential of targeting immune pathways to combat PD. The strategic modulation of neutrophils presents a novel avenue for intervention, aiming to rebalance the periodontal microenvironment and halt disease progression. This research endeavors to extend beyond the current paradigms of PD treatment, advocating for the development of targeted immunomodulatory therapies that can effectively restore and preserve periodontal health. This study stands as a testament to the promise of precision medicine in dentistry, with the potential to revolutionize periodontal therapy and improve patient outcomes.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
|
| Date: |
13 May 2024 |
| Date Type: |
Publication |
| Defense Date: |
27 March 2024 |
| Approval Date: |
13 May 2024 |
| Submission Date: |
4 April 2024 |
| Access Restriction: |
2 year -- Restrict access to University of Pittsburgh for a period of 2 years. |
| Number of Pages: |
67 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
School of Dental Medicine > Dental Science |
| Degree: |
MS - Master of Science |
| Thesis Type: |
Master's Thesis |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
Periodontitis, neutrophils, macrophages, immunomodulation, CCL2 |
| Date Deposited: |
13 May 2024 12:34 |
| Last Modified: |
13 May 2024 12:36 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/46021 |
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