Understanding chemokines in the oral mucosa

Reilly, Robert James Rees (2023) Understanding chemokines in the oral mucosa. PhD thesis, University of Glasgow.

Abstract

Introduction: The gingiva is a unique barrier tissue exposed to masticatory forces, microbial insult, and food and airborne antigens. A bespoke immune network is essential to maintain homeostasis in this dynamic environment. Leukocytes, including CD4+ T cells, are central to maintaining oral health and are pivotal in oral disease pathogenesis. There is currently limited insight into the molecular mechanisms that regulate cellular recruitment to the gingival barrier. Chemokines, the main in vivo regulator of leukocyte recruitment, are likely to orchestrate cellular recruitment to the gingiva as they are crucial to maintaining homeostasis at other barrier tissues. This thesis sought to define the chemokine landscape in healthy gingiva, compare chemokine expression between health and periodontitis and characterise the chemokine receptor repertoire of CD4+ T cells in the gingiva.

Results: The chemokine landscape in the gingiva differed from the skin and small intestine. In gingival tissues, the CXCL12/CXCL14/CXCR4/ACKR3 axis was highly expressed and conserved between mammalian species. The chemokine landscape was similar in health and periodontitis, except for neutrophil chemoattractants and CXCL14, which were upregulated and downregulated, respectively, in periodontitis. The chemokine receptor CXCR4 was highly expressed on gingival CD4+ T cells and upregulated compared to lymph node CD4+ T cells. Chemokine receptors responsible for skin and small intestine homing were minimally expressed on gingival CD4+ T cells.

Conclusions: The gingival chemokine landscape is unique compared to other barrier tissues. The mechanisms regulating CD4+ T cells migration to gingiva are likely distinct from the skin and small intestine. The similarity in chemokine expression between health and periodontitis may reflect the need for constant immunosurveillance at the gingival barrier. These findings, in the context of previously published data, suggest a prominent role for CXCL12/CXCL14/CXCR4 and ACKR3 in regulating homeostasis at the oral barrier. Further investigation is warranted to understand the precise role of this axis in more detail, and this may identify novel therapeutic targets to treat immune-mediated oral disease.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Subjects: Q Science > QR Microbiology; Q Science > QR Microbiology > QR180 Immunology
• Colleges/Schools: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Funder's Name: Medical Research Council (MRC)
• Supervisor's Name: Culshaw, Professor Shauna, Graham, Professor Gerard and Hayes, Dr. Alan
• Date of Award: 2023
• Depositing User: Theses Team
• Unique ID: glathesis:2023-83729
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 21 Jul 2023 14:03
• Last Modified: 21 Jul 2023 14:06
• Thesis DOI: 10.5525/gla.thesis.83729
• URI: https://theses.gla.ac.uk/id/eprint/83729