■系统性红斑狼疮(SLE)是一种自身免疫性疾病,其中循环免疫复合物可引起不同类型的肾小球肾炎,根据免疫沉积物和肾小球细胞损伤的类型。增生性病变代表狼疮性肾炎(LN)的最严重形式,通常导致肾衰竭和死亡。粘膜相关的不变T(MAIT)细胞是先天样T细胞的子集,其识别来自核黄素合成途径的微生物衍生的配体。尽管在外周血中丰富,MAIT细胞在粘膜和发炎组织中富集。虽然以前的研究已经报道了关于SLE患者血液中MAIT细胞频率较低的一致结果,目前尚不知道MAIT细胞功能和LN严重程度及结局的相关信息.
■在当前的研究中,我们通过流式细胞术分析了26例LN患者和16例健康对照组的外周血MAIT细胞的基线表型和功能。
■我们观察到LN患者血液中MAIT细胞频率显著降低。来自患者的MAIT细胞在迁移方面具有改变的表型,增殖和分化标记,特别是在最严重的LN形式中。PMA/离子霉素刺激的MAIT细胞分泌效应分子的频率,如促炎性IL-17和细胞毒性蛋白颗粒酶B,在LN患者中更高。免疫抑制治疗后肾脏完全缓解的患者有更高的MAIT细胞频率,纳入时增殖标记Ki-67和颗粒酶B(GzB)的表达降低。值得注意的是,GzB生产定义了完全缓解的预测模型。
■我们在此报告,血液MAIT细胞在严重的狼疮性肾炎中表现出促炎和细胞毒性功能,这可能是发病机制的作用,但与系统性狼疮活动无关.最后,MAIT细胞的低细胞毒性可能是诱导治疗一年后狼疮性肾炎缓解的一个有希望的预后因素。
Systemic lupus erythematosus (SLE) is an autoimmune disease in which circulating immune complexes can cause different types of glomerulonephritis, according to immune deposits and to the type of glomerular cell injury. Proliferative lesions represent the most severe form of lupus nephritis (LN) and often lead to kidney failure and death. Mucosal-associated invariant T (MAIT) cells are a subset of innate-like T cells that recognize microbial-derived ligands from the riboflavin synthesis pathway. Although abundant in peripheral blood, MAIT cells are enriched in mucosal and inflamed tissues. While previous studies have reported concordant results concerning lower MAIT cell frequencies in the blood of SLE patients, no information is known about MAIT cell function and LN severity and outcome.
In the current study, we analyzed the baseline phenotype and function of peripheral blood MAIT cells by flow cytometry in 26 patients with LN and in a control group of 16 healthy individuals.
We observe that MAIT cell frequencies are markedly reduced in blood of LN patients. MAIT cells from patients have an altered phenotype in terms of migration, proliferation and differentiation markers, notably in most severe forms of LN. Frequencies of PMA/ionomycin stimulated MAIT cells secreting effector molecules, such as proinflammatory IL-17 and cytotoxic protein granzyme B, are higher in LN patients. Patients undergoing a complete renal remission after immunosuppressive therapy had higher MAIT cell frequency, lower expression of proliferation marker Ki-67 and granzyme B (GzB) at inclusion. Remarkably, GzB production defines a predictive model for complete remission.
We report here that blood MAIT cells display proinflammatory and cytotoxic function in severe lupus nephritis which may play a pathogenesis role, but without association with systemic lupus activity. Finally, low cytotoxic profile of MAIT cells may represent a promising prognostic factor of lupus nephritis remission one year after induction therapy.