OLP is an autoimmune inflammatory disease involving multiple types of immune cells. In the present study, we evaluated the phenotypes and cytokine expression profiles of MAIT cells in OLP patients with different stages. To our knowledge, this is the first report to extensively describe whether the characteristics of circulating MAIT cells in OLP patients are affected by different periods of onset.
Several studies have shown that patients with autoimmune diseases such as MS, SLE, and RA have a lower frequency of MAIT cells. The MAIT cell frequency was also correlated with disease severity in autoimmune liver diseases and bronchial asthma[21, 22]. In the present study, the frequency of MAIT cells in the OLP group was decreased, and no significant difference was observed between the recent onset and long-term onset groups, suggesting that the MAIT cell alterations in the OLP group were not affected by the duration of onset. Compared with the healthy control group, the frequency of CD8+MAIT cells decreased in the long-term OLP group, and there was an increasing trend in the expression of DN MAIT cells, indicating that the dominant cell toxicity function of the MAIT cells in the onset of OLP may change as the disease progresses over time. This could be influenced by late-stage treatment intervention.
In individuals with recent-onset OLP, MAIT cells harbored an activated phenotype (CD69 and CD38 upregulation). MAIT cells exhibit an activated and exhausted phenotype, characterized by high expression of CD69 and PD-1 in adults with long-term OLP. This demonstrates that the alterations in phenotype are more pronounced in adults with long-term OLP compared with those with recent-onset OLP. Moreover, the expression of CD69 and CD38 on MAIT cells positively correlated with disease activity in both recent-onset and long-term OLP. These findings suggest that activated MAIT cells may augment the pathological condition of OLP. Of note, CD69+, CD38+, and PD-1+ MAIT cell frequencies negatively correlated with MAIT cell frequency in both healthy controls and adults with long-term OLP but not in those with recent-onset OLP. This suggests that MAIT cell profiles may differ as the disease evolves.
It is well established that MAIT cells can release pro-inflammatory cytokines in Th1 or Th17 patterns in response to TCR mediation and that the pathogenesis of several disorders is influenced by the IL-17 released by MAIT cells[23–25]. Previous studies have reported that MAIT cells produced high levels of IL-17, but there was no significant difference between the OLP and HC group[17]. In contrast, our findings found that participants with recent-onset OLP exhibited an elevated production of proinflammatory cytokines IL-17A and long-term OLP also showed a similar trend, but there was no significant difference between the OLP groups. This suggests that MAIT cells may exert a pro-inflammatory role through a Th17-type immune response during the pathogenesis of OLP. In addition, GzB-producing MAIT cells were increased in individuals with long-term OLP in comparison with healthy donors, indicating that GzB may be involved in the apoptosis of basal keratinocytes in OLP as the disease progresses.
Collectively, adults with recent-onset OLP displayed higher frequencies of CD69+ and CD38+ MAIT cells, as well as higher levels of the proinflammatory cytokine IL-17A, indicating an activated nature in their MAIT cells. Individuals with prolonged OLP display an active and depleted phenotype of MAIT cells, which is marked by elevated granzyme B production and high expression of CD69 and PD-1. Our study reinforces the potential of MAIT cells as a biomarker of disease progression, but there are still limitations to be considered, such as relatively small sample size and lack of longitudinal experimental design. Subsequent studies will include more clinical indicators to explore the predictive value for the long-term prognosis of OLP patients.