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A Tissue-Engineered Model of T-Cell-Mediated Oral Mucosal Inflammatory Disease
Asma El-Howati1, Jake G Edmans2, Martin E Santocildes-Romero3
1School of Clinical Dentistry, University of Sheffield, Sheffield, United Kingdom; Department of Oral Medicine, Faculty of Dentistry, University of Benghazi, Benghazi, Libya.
The Journal of Investigative Dermatology
|October 4, 2024
Summary
Researchers developed a novel tissue-engineered model of oral lichen planus using T-cells and oral mucosal equivalents. This model replicates disease pathogenesis and shows promise for testing new treatments for this common inflammatory condition.
Area of Science:
- Immunology
- Tissue Engineering
- Dermatology
Background:
- T-cell-mediated inflammatory conditions like oral lichen planus (OLP) are prevalent.
- Developing new OLP treatments is challenging due to a lack of suitable experimental models.
Purpose of the Study:
- To create a tissue-engineered oral mucosal equivalent model with T-cells to study OLP pathogenesis.
- To establish a platform for evaluating potential OLP therapeutics.
Main Methods:
- Isolated and polarized peripheral blood CD4+ and CD8+ T-cells into T helper 1 (Th1) and cytotoxic T cells.
- Constructed oral mucosal equivalents using oral keratinocytes on a fibroblast-populated hydrogel.
- Developed a disease model by combining the oral mucosal equivalent with T-cells and stimulating with inflammatory cytokines (IFN-γ, TNF-α).
Main Results:
- The model demonstrated increased inflammatory cytokine and chemokine secretion (CCL5, CXCL9, CXCL10) upon stimulation.
- Histological analysis revealed tissue damage, including cleaved caspase-3 expression and altered laminin-5.
- Inhibitors (Jak, KCa3.1 channel blockers, clobetasol) reduced cytokine release and tissue damage.
Conclusions:
- A functional T-cell-mediated oral inflammatory disease model was successfully developed.
- This model can be used to investigate OLP pathogenesis mechanisms.
- The model serves as a valuable platform for testing novel therapeutic agents and treatment strategies for OLP.
