背景:常见的具有异常粘膜免疫的原发性肾小球肾炎是IgA肾病(IgAN)。滤泡辅助性T细胞(TFH)在调节B细胞分化中至关重要。派尔斑块(PPs)是IgA+成浆细胞分化的主要位点。
目的:我们的研究旨在探讨TFH细胞在IgA肾病病因中的潜在作用。
方法:在IgAN小鼠模型的PPs中,TFH细胞的比例,B220+IgA+,B220+IgM+,和B220-IgA+淋巴细胞进行评估。然后,我们使用Westernblot评估PPs中Bcl-6,Blip-1和IL-21蛋白的表达,并使用RT-PCR评估IL-21和TGF-1mRNA的表达。TFH细胞与脾细胞共培养以测定TFH细胞上IL-21的程度和活化标记物CD69的比例。将来自患有IgAN的儿童的幼稚B细胞(CD27-IgD+)与TFH细胞相关细胞因子一起培养。检测上清液以评估半乳糖缺陷型IgA1(Gd-IgA1)的排泄。
结果:IgAN小鼠在TFH细胞上的IL-21和CD69程度明显高于对照组,以及更高百分比的B220+IgA+,B220+IgM+,B220+IgA+,PPs中的TGF-1、IL-21mRNA和Bcl-6、IL-21蛋白。上清液和IgAN阳性儿童血清中的Gd-IgA1水平明显高于健康对照组(P<0.05)。PPs提供微环境以诱导分泌IgA的成浆细胞的产生。
结论:TFH细胞可能是诱导B细胞分化为分泌IgA的浆母细胞并产生Gd-IgA1的关键调节剂,在IgAN的发病中起重要作用。它可能是未来新的治疗靶点。
BACKGROUND: Common primary glomerulonephritis with aberrant mucosal immunity is IgA nephropathy (IgAN). T follicular helper (TFH) cells are essential in regulating B cell differentiation. Peyer\'s patches (PPs) are the main site where IgA+ plasmablasts differentiate.
OBJECTIVE: Our study aimed to investigate the TFH cell\'s potential contribution to the etiology of IgA nephropathy.
METHODS: In PPs from IgAN mouse models, the ratio of the TFH cell, B220+IgA+, B220+IgM+, and B220-IgA+ lymphocytes were assessed. Then, we used Western blot to assess the expression of Bcl-6, Blimp- 1, and IL-21 proteins in PPs and used RTPCR to assess the expression of IL-21 and TGF-β1 mRNA. TFH cells coculture with spleen cells to measure the degree of IL-21 and the ratio of activation marker CD69 on the TFH cells. Naive B cells (CD27-IgD+) from children suffering from IgAN were cultured with TFH cell-related cytokines. The supernatant was detected to assess the excretion of galactose-deficient IgA1 (Gd-IgA1).
RESULTS: IgAN mice developed noticeably increased degrees of IL-21 and CD69 on TFH cells than controls did, as well as higher percentages of B220+IgA+, B220+IgM+, B220+IgA+, TGF- β1, and IL-21 mRNA and Bcl-6, IL-21 proteins in PPs. The Gd-IgA1 level in the supernatant and IgAN- positive children\'s serum were noticeably higher than those of the healthy controls (P < 0.05). PPs provide the microenvironment to induce the production of IgA-secreting plasmablasts.
CONCLUSIONS: TFH cells may be a key moderator to induce B cell differentiation into IgAsecreting plasmablasts and produce Gd-IgA1, which plays a significant part in IgAN\'s pathogenesis. It could be a new therapeutic target in the future.