In our study, the association between cytokines, MAIT cells and MDSCs were explored in PCOS patients. In the last decades, abundant evidences have indicated that immune responses play an important role in PCOS, including the immunological activities of different T-cells, macrophages and associated inflammatory factors [6–11]. However, till now there is no study that showed investigation of MAIT cells and MDSCs in PCOS patients. In this study, we revealed that the disorders of circulatory MAIT cells as well as MDSCs might be an immunological pathogenesis for PCOS and was associated with metabolic dysfunction.
It has been reported that the abnormality of Th17 cells percentage was associated with PCOS [29]. Due to the same secretion of IL-17, MAIT cells have been reported to have a similar function of Th17 cells [30]. In this study, a decreased frequency of CD8+MAIT cells in PCOS patients was revealed. Moreover, CD38+CD8+MAIT cells, known as activated MAIT cells, were also reduced. MAIT cells are divided into three subgroups, CD8+MAIT cells, CD4+MAIT cells, and CD8−CD4−MAIT cells [15]. Our results indicated that the impaired frequency and function of CD8+MAIT cells might have a close link with PCOS. Early studies have suggested that CD8+MAIT cells played a protective role in some diseases [31, 32]. Consistent with previous studies, our study also revealed the protective role of CD8+MAIT cells in PCOS. Nonetheless, CD4+MAIT cells displayed an expansion in PCOS. It has been known that the functional roles and frequencies of MAIT cells differ between different subsets and different diseases [33, 34]. In this study, our results also support the distinct roles of CD8+MAIT and CD4+MAIT cells. Recently, PCOS was also recognized as a chronic inflammatory disease [35, 36]. Therefore, our findings would suggest that the protective role of CD8+MAIT cells in PCOS are weakened, which is similar to the results from other chronic inflammatory diseases.
Two of the major problems from patients with PCOS are overweight and obesity. In our study, we found that with the increase of BMI, the frequencies of CD8+MAIT cells and CD38+CD8+MAIT cells decreased. Whereas, the proportion of CD4 + MAIT cells displayed increased levels. Previous researches have depicted that obese adults displayed a depletion of circulating MAIT cells [20, 21]. Touch et al. have revealed that obese human showed an impaired frequency of MAIT cells [37]. Recent study investigated by Li et al. has suggested that considerable decrease of MAIT cells frequency and distinct dysfunctional state of MAIT cells in obese patients [38]. CD8 + MAIT cells were the majority of MAIT cells, we implied that the lipid metabolic disorder was mainly affected by the decreased amount and weakened function of CD8+ MAIT cells in PCOS patients [16]. We indicated that the reduction of CD8 + MAIT cells might promote the development of obesity in PCOS patients.
MDSCs have been indicated to have a close relation with MAIT cells in various pathological processes [28]. Haeryfar et al. suggested that MAIT cells could induce MDSCs [26]. Nevertheless, a direct connection between MAIT cells and MDSCs has not been identified in PCOS. In our study, we found a significant reduction of MDSCs and a positive relationship between MAIT cells and MDSCs in the PB of PCOS patients. One explanation would be that lessened MAIT cells have an impaired function of induction of MDSCs. Till now there are no studies about the role of MDSCs in PCOS, however, another group of immunosuppressive cells, Tregs, has been indicated to be reduced in PCOS patients [11, 39]. Based on the immunosuppressive properties of MDSCs and Tregs, the two populations are expected to share a similar role in different diseases [40, 41]. Reduced immunosuppression is a key factor in the overreaction in inflammatory response. As mentioned previously, patients with PCOS have a strong chronic inflammatory background. Therefore, we suggested that an impaired immunosuppressive microenvironment with reduced MDSCs might be a cause of long-term chronic inflammation in PCOS.
Furthermore, our findings also revealed that PCOS patients with disorders of glucose metabolism had a strong reduction of MDSCs and Mo-MDSCs. What’s more, with the progression of glucose metabolic dysfunction, the frequencies of MDSCs and Mo-MDSCs decreased. The roles of MDSCs in metabolic diseases have been widely studied. Yin et al. have demonstrated that transferred MDSCs could down-regulate autoimmune responses and prevent diabetes onset in mice model [42]. Researchers have previously clarified that MDSCs could improve metabolic dysfunctions and act as a protector in obesity [43]. Combined with these results, our study indicated that a decreased frequency of MDSCs and Mo-MDSCs might induce the occurrence of metabolic dysfunction in PCOS patients.