Circulating mucosal-associated invariant T cell alterations in adults with recent-onset and long-term oral lichen planus

Abstract

Background: Mucosal-associated invariant T (MAIT) cells play key roles in many inflammatory diseases. However, their effects on the long-term course of oral lichen planus (OLP) and recent-onset OLP remain unclear. In this study, we aimed to investigate the function of MAIT cells in the different processes of OLP and to explore the immunological background of this disease.

Methods: The frequency, phenotype, cytokine secretion, and clinical relevance of MAIT cells were investigated. MAIT cells were collected from the peripheral blood of 14 adults with recent-onset OLP (7-120 days after disease onset) and 16 adults with long-term course OLP (>2 years after diagnosis) using flow cytometry and compared with 15 healthy blood donors. Statistical analyses were performed using the GraphPad Prism software.

Results: MAIT cells from adults with recent-onset OLP exhibited an activated phenotype, as indicated by an increased frequency of CD69⁺ (p < 0.05) and CD38⁺MAIT cells (p < 0.01) and elevated production of the proinflammatory cytokine IL-17 A (p < 0.01), compared with healthy adult donors. In adults with long-term OLP, MAIT cells exhibited an activated and exhausted phenotype, characterized by high expression of CD69 (p < 0.01) and PD-1 (p < 0.001) and increased production of granzyme B released (p < 0.01). Compared with recent-onset OLP patients, long-term OLP patients showed a decreased production of CD8⁺, and CD4^-CD8^- cells, but an increase in PD-1⁺ production (p < 0.05).

Conclusions: Circulating MAIT cells exhibited activation in OLP patients across varying disease durations. Given that PD-1 expression is elevated in adults with long-term OLP, it is reasonable to infer that circulating MAIT cells in long-term OLP may exhibit a more exhausted state than those in recent-onset OLP.

Keywords: Functional profile; Immunoregulatory activity; Mucosal-associated invariant T cells (MAIT cells); Oral lichen planus (OLP); Phenotypes.

Fig. 1

Frequency alterations of circulating MAIT and its different subsets in OLP patients at different stages. Multicolor flow cytometric analyses of CD3 + TCR Vα7.2 + CD161 high T-cells in peripheral whole blood samples of patient with recent-onset OLP (n = 14), long term OLP (n = 16), and healthy controls (n = 15), which gender- and age-matched. (a) Representative flow cytometry plots of three groups’ samples showing the gating strategy to identify TCR Vα7. 2 + CD161 high T-cells (referred to here as MAIT cells). (b) Summary frequency of peripheral blood MAIT cells from patients with recent-onset(n = 14) or long-term OLP (n = 16) and healthy controls (n = 15). (c-d) Summary frequency of CD8+ (c) or CD4-CD8- (d) circulating MAIT cells from patients with recent-onset(n = 14) or long-term OLP (n = 16) and healthy controls (n = 15). *p < 0.05; **p < 0.01; ***p < 0.001; ns, not statistically significant. Correlations were calculated using the Spearman’s correlation analysis. DN, CD4-, CD8- double negative. HC, healthy controls; LT, long-term; RO, recent-onset; OLP, Oral lichen planus

Fig. 2

The phenotype alterations of circulating MAIT cells in OLP patients at different stages. (a ∼ e) Summary frequency of CD69+ (a), CD38+ (b), HLA-DR+ (c), PD-1+ (d), or Tim-3+ (e) MAIT cells in healthy donors (n = 15) and participants with recent-onset (n = 14) or long-term OLP (n = 16). (f ∼ j) Correlation between frequency of circulating MAIT cells and frequency of CD69+ (f), CD38+(g), HLA-DR+ (h), PD-1+ (i) or Tim-3+ (j) MAIT cells in healthy donors and participants with recent-onset or long-term OLP. *p < 0.05; **p < 0.01; ***p < 0.001; ns, not statistically significant. Correlations were calculated using the Spearman’s correlation analysis. HC, healthy controls; LT, long-term; RO, recent-onset; OLP, Oral lichen planus

Fig. 3

The phenotype alterations of peripheral blood MAIT cells in OLP at different stages and its clinical significance. (a–c) Correlations between the percentage of CD69+ (a), CD38+ (b), or HLA-DR+ (c) MAIT cells and RAE scores in participants with recent-onset (n = 14) or long-term (n = 16) OLP. (d) The correlation between the various phenotypes of MAIT cell in participants with recent-onset and long-term OLP and the RAE scores is displayed in a heatmap with r-values. (e) Correlograms of circulating MAIT cell frequency and marker expression in healthy donors and participants with recent-onset (n = 14) or long-term OLP(n = 16)

Fig. 4

Functional profile of MAIT cells in peripheral blood of patients with OLP. To assess the production of cytokines GzB, IFN-γ, TNF-α, IL-17 A, and IL-22 of OLP MAIT after activation with PMA and ionomycin. Detection and difference of MAIT cell-associated cytokines from blood of adults with recent-onset (n = 14) or long-term (n = 16) OLP and healthy donors (n = 15) after PMA/ionomycin stimulation. Data were expressed as mean ± SD. *p < 0.05; **p < 0.01. OLP, Oral lichen planus. GzB, granzyme B