METHODS: Blood samples from HSP patients and HDs were assessed by flow cytometry and single-cell RNA sequencing to analyze the proportion, phenotype, and function of MAIT cells. Th-cytokines in the serum of HSP patients were analyzed by CBA. IgA in cocultured supernatant was detected by CBA to analyze antibody production by B cells.
RESULTS: The percentage of MAIT cells in HSP patients was significantly reduced compared with that in HDs. Genes related to T cell activation and effector were up-regulated in HSP MAIT cells, indicating a more activated phenotype. In addition, HSP MAIT cells displayed a Th2-like profile with the capacity to produce more IL-4 and IL-5, and IL-4 was correlated with IgA levels in the serum of HSP patients. Furthermore, CD40L was up-regulated in HSP MAIT cells, and CD40L+ MAIT cells showed an increased ability to produce IL-4 and to enhance IgA production by B cells.
CONCLUSIONS: Our data demonstrate that MAIT cells in HSP patients exhibit an activated phenotype. The enhanced IL-4 production and CD40L expression of MAIT cells in HSP patients could take part in the pathogenesis of HSP.
方法:通过流式细胞术和单细胞RNA测序评估来自HSP患者和HDs的血液样本,以分析比例,表型,MAIT细胞的功能。用CBA分析HSP患者血清中的Th-细胞因子。通过CBA检测共培养上清液中的IgA以分析B细胞的抗体产生。
结果:与HDs相比,HSP患者的MAIT细胞百分比明显降低。与T细胞活化和效应相关的基因在HSPMAIT细胞中上调,表明更激活的表型。此外,HSPMAIT细胞表现出Th2样特征,具有产生更多IL-4和IL-5的能力,并且IL-4与HSP患者血清中的IgA水平相关。此外,CD40L在HSPMAIT细胞中上调,和CD40L+MAIT细胞显示增加的产生IL-4和增强B细胞产生IgA的能力。
结论:我们的数据表明,HSP患者的MAIT细胞表现出活化的表型。HSP患者MAIT细胞的IL-4产生和CD40L表达增强可能参与了HSP的发病机制。