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Updated: Jul 9, 2026
Intravital Imaging of Intraepithelial Lymphocytes in Murine Small Intestine
Published on: June 24, 2019
GPR55 negatively regulates CD8+ intraepithelial lymphocyte migration dynamics in oral lichen planus
Dongyang Zhou1, Gang Zhou2,3
1State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
Insights
Researchers found that GPR55 negatively regulates intraepithelial lymphocyte (IEL) migration in oral lichen planus (OLP). Blocking GPR55 enhances IEL migration, offering a potential therapeutic strategy for OLP by preserving mucosal barrier integrity.
Area of Science:
- Immunology
- Cell Biology
- Dermatology
Background:
- Oral lichen planus (OLP) is a common T-cell mediated inflammatory condition affecting oral mucosa.
- The precise molecular mechanisms of intraepithelial lymphocyte (IEL) migration and interaction with keratinocytes in OLP are not fully understood.
Purpose of the Study:
- To investigate the role of CD8αα expression and G protein-coupled receptor 55 (GPR55) in IEL migration within OLP lesions.
- To explore the therapeutic potential of targeting GPR55 for OLP treatment.
Main Methods:
- Analysis of IEL subsets (TCRαβ+CD8αα+, TCRγδ+CD8αα+) in OLP lesions.
- Live-cell imaging to assess IEL migratory kinetics.
- Cytokine neutralization assays (IL-17A, IFN-γ).
- Pharmacological blockade of GPR55 and assessment of IEL proliferation, apoptosis, and migration.
Main Results:
- CD8αα expression on IELs facilitates epithelial migration.
- CD8αα+ IELs in OLP lesions produce elevated IL-17A and IFN-γ, which promote IEL recruitment.
- GPR55 is highly expressed on CD8αα+ IELs and acts as a negative regulator of IEL transmigration.
- GPR55 blockade enhances IEL migration and cell-to-cell contact with keratinocytes.
Conclusions:
- GPR55 restricts CD8+ IEL migration into the oral epithelium in OLP.
- Targeting GPR55 may offer a novel therapeutic approach to modulate IEL activity and maintain mucosal barrier function in OLP.
Abstract:
Oral lichen planus (OLP) is a prevalent T-cell-mediated inflammatory disease of the human oral mucosa. Intraepithelial lymphocytes (IELs) engage in close cellular interactions with epithelial keratinocytes; however, the molecular mechanisms governing their migration and dynamic crosstalk with the epithelium remain incompletely defined. Here, we demonstrate that TCRαβ+CD8αα+ and TCRγδ+CD8αα+ IELs represent two key CD8αα+ subsets within the total IEL population in OLP lesions. Live-cell imaging revealed that CD8αα⁻ IELs exhibited slower migratory kinetics compared with their CD8αα+ counterparts, confirming that surface CD8αα expression facilitates epithelial migration of CD8+ IELs. Within inflamed OLP mucosa, CD8αα+ IELs produce markedly elevated levels of the pro-inflammatory cytokines IL-17 A and IFN-γ. Neutralization of these two cytokines with specific antibodies reduced the migratory capacity of both CD8αα+ and CD8αα⁻ IELs, indicating that the inflammatory microenvironment promoted CD8+ IEL recruitment into lesional epithelium. GPR55 was highly expressed in CD8αα+ IELs. Pharmacological blockade of GPR55 suppressed proliferation and significantly induced apoptosis in both IEL subsets. Furthermore, GPR55 antagonism robustly enhanced IEL migration and strengthened cell-to-cell contacts between IELs and oral keratinocytes (KCs). These findings identify GPR55 as a negative regulator that restricts transmigration of CD8+ IELs into the oral epithelium. Targeted GPR55 inhibition may represent a promising strategy to modulate aberrant IEL activity and preserve mucosal epithelial barrier integrity in OLP.