Fractalkine mediates lymphocyte inflammation and tubulointerstitial lesions by modifying the Treg/Th17 balance in lupus-prone MRL/lpr mice.
Fractalkine mediates lymphocyte inflammation and tubulointerstitial lesions by modifying the Treg/Th17 balance in lupus-prone MRL/lpr mice.
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Fractalkine 通过改变狼疮倾向 MRL/lpr 小鼠的 Treg/Th17 平衡来介导淋巴细胞炎症和肾小管间质病变。
DOI：
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发表时间：
2020-10
影响因子：
2.2
通讯作者：
Liao Pinhu
中科院分区：
文献类型：
--
作者：
Dongdong Fu;Jingxue Ma;Qiming Gong;Soulixay Senouthai;Junjie Wang;Yanwu You;Liao Pinhu
本研究首先分析了Fractalkine（FKN）在狼疮性肾炎（LN）患者血清中的表达水平及外周血Treg细胞的分布，并探讨FKN与Treg细胞、系统性红斑狼疮疾病活动指数2000（SLEDAI-2K）的相关性。随后，我们探讨了FKN在狼疮模型小鼠肾小管间质病变（TILs）和调节性T（Treg）细胞/辅助性T（Th）17细胞平衡中的特定作用。用抗FKN抗体（aFKN）、重组FKN（rFKN）或同种型抗体（IgG）处理MRL/MpJ-Faslpr/J和C57 BL/6小鼠，然后检测肾脏和脾脏中TIL水平和叉头盒p3（Foxp 3）、IL-10、IL-17和IL-6表达水平在Treg和Th 17细胞比例中的变化。最后，分别用α FKN、rFKN或IgG干预小鼠脾淋巴细胞转化生长因子（TGF）-β和白细胞介素（IL）-2后的极化T淋巴细胞和IL-6、TGF-β、IL-23、抗干扰素和抗IL-4的Th 17细胞。结果显示，FKN表达水平与SLEDAI-2K呈正相关，与Treg细胞分布呈负相关。狼疮模型小鼠经aFKN治疗后，肾脏损害延迟，TIL形成减少，Foxp 3和IL-10水平上调，肾组织中IL-17和IL-6水平下调，Th 17细胞亚群和Treg细胞亚群减少，脾脏中增加，而rFKN治疗小鼠则有相反的作用。此外，在体外实验中，aFKN干预极化细胞后，发现Th 17细胞中IL-17和IL-6的表达水平下调，Tcells中Foxp 3和IL-10的表达水平上调，而rFKN处理具有相反的效果。这些结果表明，FKN参与并促进SLE靶器官损伤，包括：炎症因子和肾脏TIL的分泌，最重要的是，这些作用可能是由于调节Treg/Th 17细胞平衡。
In this study, we first analyzed the expression level of fractalkine (FKN) in the serum of patients with lupus nephritis (LN) and the distribution of peripheral blood Treg cells, and explored FKN and Treg cells, systemic lupus erythematosus disease activity index 2000 (SLEDAI-2K) correlation. Subsequently, we explored the specific role of FKN in tubule interstitial lesions (TILs) and regulatory T (Treg) cells/T helper (Th) 17 cell balance in lupus model mice. Treated with an anti-FKN antibody (aFKN), recombinant FKN (rFKN), or an isotype antibody (IgG) in MRL/MpJ-Faslpr/J and C57BL/6 mice, and then detected TIL level and forkhead box p3 (Foxp3), IL-10, IL-17 and IL-6 expression levels in the kidney and spleen in the proportion of Treg and Th17 cells. Finally, then use aFKN, rFKN, or IgG to intervene in polarized Tregs with IL-6, TGF-β, IL-23, anti-interferon, and Th17 cells with anti-IL-4 after transforming to transform growth factor (TGF)-β and interleukin (IL)-2 in isolated mouse spleen lymphocytes. The results showed that the expression level of FKN was positively correlated with SLEDAI-2K and negatively correlated with the distribution of Treg cells. After treatment with aFKN in lupus model mice, kidney damage was delayed, TIL formation was reduced, Foxp3 and IL-10 levels were up-regulated, IL-17 and IL-6 levels were down-regulated in renal tissues, Th17 cell subsets and Treg cell subsets were reduced The increase is in the spleen, and rFKN treatment has the opposite effect in mouse. In addition, after interfering with polarized cells by aFKN, it was found that IL-17 and IL-6 expression levels were down-regulated in Th17 cells, Foxp3 and IL-10 levels in Tregs were up-regulated, and rFKN treatment had the opposite effect in vitro. These results indicate that FKN participates in and promotes SLE target organ damage including: secretion of inflammatory factors and renal TIL, and most importantly, these effects might have been due to modification of the Treg/Th17 cell balance.
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影响因子：
7.3
作者：
Hall BM;Tran GT;Verma ND;Plain KM;Robinson CM;Nomura M;Hodgkinson SJ
通讯作者：
Hodgkinson SJ
影响因子：
12.4
作者：
Hong JY;Kim M;Sol IS;Kim KW;Lee CM;Elias JA;Sohn MH;Lee CG
通讯作者：
Lee CG
DOI：
10.12659/msm.908406
发表时间：
2018-08-03
期刊：
Medical science monitor : international medical journal of experimental and clinical research
影响因子：
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作者：
Zhao P;Miao J;Zhang K;Lv M;Han Q;Zhu P
通讯作者：
Zhu P
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影响因子：
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作者：
Jin X;Su R;Li R;Cheng L;Li Z
通讯作者：
Li Z
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影响因子：
4.6
作者：
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通讯作者：
Zeng Q