NK1.1- natural killer T cells upregulate interleukin-17 expression in experimental lupus nephritis
NK1.1- natural killer T cells upregulate interleukin-17 expression in experimental lupus nephritis
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DOI：
10.1152/ajprenal.00252.2020
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发表时间：
2021-05-01
影响因子：
4.2
通讯作者：
Yang, Seung Hee
中科院分区：
文献类型：
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作者：
An, Jung Nam;Ryu, Seungwon;Yang, Seung Hee
分泌IL-17的不变自然杀伤T细胞(NKT)参与多种炎症性疾病。然而，它们在狼疮性肾炎(LN)中的作用还没有完全确定。采集LN和肾小球肾炎患者及健康对照的肾组织标本，发现LN患者血细胞中IL-17(+)NKT细胞数升高，肾组织中IL-17表达升高。将实验性自身免疫性LN的小鼠模型与亲本品系(NKT缺陷的B6.CD1d(-/-)小鼠)进行比较，发现蛋白尿、疾病严重程度和组织病理学得到改善，趋化因子(C-X-C基序)配体16和T细胞受体-α变量14的表达水平降低。B6CD1d(-/-)小鼠的脾和肾脏也显示出炎症标志物和IL-17的下调。在与肾小球系膜细胞和NKT细胞的共同培养中，α-半乳糖神经酰胺处理后炎症标志物和IL-17上调，IL-17阻断抗体处理后下调。这在杀伤细胞凝集素样受体B亚家族成员1C(NK1.1)(-)NKT细胞中最为突出。因此，IL-17在LN中上调。NKT细胞的激活主要通过NK1.1(-)NKT细胞在系统和肾脏中调节IL-17相关的免疫反应。分泌IL-17的NK1.1(-)NKT细胞可作为狼疮性肾炎的诊断和治疗靶点。值得注意的是，这项研究对文献有重要贡献，因为我们的结果表明IL-17在狼疮性肾炎中表达上调，自然杀伤T(NKT)细胞参与其发病机制。NKT细胞的激活调节IL-17相关的免疫反应，无论是在系统还是在肾脏中，这主要涉及NK1.1(-)NKT细胞。此外，分泌IL-17的NK1.1(-)NKT细胞可作为狼疮性肾炎的诊断和治疗靶点。
Interleukin (IL)-17-secreting invariant natural killer T (NKT) cells are involved in several inflammatory diseases. However, their role in lupus nephritis (LN) has not been fully characterized. Samples from patients with LN or glomerulonephritis and healthy controls were obtained, and elevated IL-17(+) NKT cell numbers and IL-17 expression were observed in blood cells and kidneys, respectively, in patients with LN. Comparison of a mouse model of experimental autoimmune LN with the parental strain (NKT-deficient B6.CD1d(-/-) mice) revealed improved proteinuria, disease severity, and histopathology and decreased levels of chemokine (C-X-C motif) ligand 16 and T cell receptor-alpha variable 14 expression. Spleens and kidneys of B6CD1d(-/-) mice also showed downregulation of inflammatory markers and IL-17. In coculture with renal mesangial and NKT cells, inflammatory markers and IL-17 were upregulated following alpha-galactosylceramide treatment and downregulated after treatment with IL-17-blocking antibodies. This was most prominent with killer cell lectin-like receptor subfamily B member 1C (NK1.1)(-) NKT cells. Thus, IL-17 is upregulated in LN. Activation of NKT cells regulates IL-17-related immune responses systemically and in the kidneys, primarily via NK1.1(-) NKT cells. IL-17-secreting NK1.1(-) NKT cells could serve as diagnostic and therapeutic targets for LN.NEW & NOTEWORTHY This study makes a significant contribution to the literature because our results indicate that IL-17 is upregulated in lupus nephritis and that natural killer T (NKT) cells are involved in its pathogenesis. Activation of NKT cells regulates IL-17-related immune responses, both systemically and in the kidney, and this mainly involves NK1.1(-) NKT cells. Furthermore, IL-17-secreting NK1.1(-) NKT cells could serve as a diagnostic and therapeutic target for lupus nephritis.