BACKGROUND Recent studies have demonstrated that natural killer (NK) cells can modulate other immune components and are involved in the development or progression of several autoimmune diseases. However, the roles and mechanisms of NK cells in regulating experimental autoimmune myasthenia gravis (EAMG) remained to be illustrated. METHODS To address the function of NK cells in experimental autoimmune myasthenia gravis in vivo, EAMG rats were adoptively transferred with splenic NK cells. The serum antibodies, and splenic follicular helper T (Tfh) cells and germinal center B cells were determined by ELISA and flow cytometry. The roles of NK cells in regulating Tfh cells were further verified in vitro by co-culturing splenocytes or isolated T cells with NK cells. Moreover, the phenotype, localization, and function differences between different NK cell subtypes were determined by flow cytometry, immunofluorescence, and ex vivo co-culturation. RESULTS In this study, we found that adoptive transfer of NK cells ameliorated EAMG symptoms by suppressing Tfh cells and germinal center B cells. Ex vivo studies indicated NK cells inhibited CD4+ T cells and Tfh cells by inducing the apoptosis of T cells. More importantly, NK cells could be divided into CXCR5- and CXCR5+ NK subtypes according to the expression of CXCR5 molecular. Compared with CXCR5- NK cells, which were mainly localized outside B cell zone, CXCR5+ NK were concentrated in the B cell zone and exhibited higher expression levels of IL-17 and ICOS, and lower expression level of CD27. Ex vivo studies indicated it was CXCR5- NK cells not CXCR5+ NK cells that suppressed CD4+ T cells and Tfh cells. Further analysis revealed that, compared with CXCR5- NK cells, CXCR5+ NK cells enhanced the ICOS expression of Tfh cells. CONCLUSIONS These findings highlight the different roles of CXCR5- NK cells and CXCR5+ NK cells. It was CXCR5- NK cells but not CXCR5+ NK cells that suppressed Tfh cells and inhibited the autoimmune response in EAMG models.

中文翻译：

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CXCR5阴性自然杀伤细胞通过抑制卵泡辅助性T细胞改善实验性自身免疫性重症肌无力。

背景技术最近的研究表明，自然杀伤（NK）细胞可以调节其他免疫成分，并参与几种自身免疫性疾病的发展或进程。然而，NK细胞在调节实验性自身免疫性重症肌无力（EAMG）中的作用和机制仍有待阐明。方法为了研究NK细胞在实验性自身免疫性重症肌无力体内的功能，将脾脏NK细胞过继转移至EAMG大鼠。通过ELISA和流式细胞术测定血清抗体，脾滤泡辅助性T（Tfh）细胞和生发中心B细胞。通过将脾细胞或分离的T细胞与NK细胞共培养，进一步证实了NK细胞在调节Tfh细胞中的作用。而且，表型，定位，通过流式细胞术，免疫荧光和离体共培养确定不同NK细胞亚型之间的功能差异。结果在这项研究中，我们发现NK细胞的过继转移通过抑制Tfh细胞和生发中心B细胞而改善了EAMG症状。体外研究表明，NK细胞通过诱导T细胞凋亡来抑制CD4 + T细胞和Tfh细胞。更重要的是，根据CXCR5分子的表达，NK细胞可分为CXCR5-和CXCR5 + NK亚型。与主要定位在B细胞区以外的CXCR5-NK细胞相比，CXCR5 + NK集中在B细胞区，并表现出较高的IL-17和ICOS表达水平，以及较低的CD27表达水平。体外研究表明抑制CD4 + T细胞和Tfh细胞的是CXCR5- NK细胞而不是CXCR5 + NK细胞。进一步的分析表明，与CXCR5-NK细胞相比，CXCR5 + NK细胞增强了Tfh细胞的ICOS表达。结论这些发现强调了CXCR5-NK细胞和CXCR5 + NK细胞的不同作用。在EAMG模型中，抑制Tfh细胞并抑制自身免疫应答的是CXCR5-NK细胞，而不是CXCR5 + NK细胞。