Endogenous erythropoietin has immunoregulatory functions that limit the expression of autoimmune kidney disease in mice.
Endogenous erythropoietin has immunoregulatory functions that limit the expression of autoimmune kidney disease in mice.
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DOI：
10.3389/fimmu.2023.1195662
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发表时间：
2023
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
--
作者：
重组促红细胞生成素（EPO）是一种具有促红细胞生成素功能的肾生成激素，已被证明在小鼠和人体内具有多种免疫调节作用，但EPO的生理水平是否调节体内免疫功能尚未得到评估。我们使用多西环素（DOX）诱导的EPO特异性沉默RNA （shEPOrtTAPOS）培养了能够下调EPO生成的小鼠，并将其与B6杂交。发生自发性狼疮的MRL-Faslpr/J小鼠。我们处理了这些B6。MRL/lpr shEPOrtTAPOS具有DOX和连续测量的抗dsdna抗体，通过流式细胞术分析免疫亚群，并评估B6患者6个月以上疾病活动的临床体征。MRL/lpr sheporttanos和遗传shEPOrtTANEG对照。B6。与对照组相比，MRL/lpr小鼠，Epo下调增强了抗dsdna自身抗体水平，增加了疾病严重程度和生发中心B细胞的百分比。巨噬细胞细胞内IL-6和MCP-1水平升高。我们在狼疮小鼠模型中的数据表明，内源性EPO降低T细胞和b细胞的活化和自身抗体的产生，支持EPO在生理上作为一种反调节机制来控制免疫稳态的结论。
Administration of recombinant erythropoietin (EPO), a kidney-produced hormone with erythropoietic functions, has been shown to have multiple immunoregulatory effects in mice and humans, but whether physiological levels of EPO regulate immune function in vivo has not been previously evaluated. We generated mice in which we could downregulate EPO production using a doxycycline (DOX)-inducible, EPO-specific silencing RNA (shEPOrtTAPOS), and we crossed them with B6.MRL-Faslpr/J mice that develop spontaneous lupus. We treated these B6.MRL/lpr shEPOrtTAPOS with DOX and serially measured anti-dsDNA antibodies, analyzed immune subsets by flow cytometry, and evaluated clinical signs of disease activity over 6 months of age in B6.MRL/lpr shEPOrtTAPOS and in congenic shEPOrtTANEG controls. In B6.MRL/lpr mice, Epo downregulation augmented anti-dsDNA autoantibody levels and increased disease severity and percentages of germinal center B cells compared with controls. It also increased intracellular levels of IL-6 and MCP-1 in macrophages. Our data in a murine model of lupus document that endogenous EPO reduces T- and B-cell activation and autoantibody production, supporting the conclusion that EPO physiologically acts as a counterregulatory mechanism to control immune homeostasis.
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影响因子：
7.3
作者：
Eswarappa M;Cantarelli C;Cravedi P
通讯作者：
Cravedi P
影响因子：
6.5
作者：
Ludwig, Ralf J.;Recke, Andreas;Ibrahim, Saleh M.
通讯作者：
Ibrahim, Saleh M.
狼疮的鼠标：他们告诉我们什么，什么不告诉我们。
影响因子：
3.9
作者：
Richard ML;Gilkeson G
通讯作者：
Gilkeson G
影响因子：
64.5
作者：
Premsrirut PK;Dow LE;Kim SY;Camiolo M;Malone CD;Miething C;Scuoppo C;Zuber J;Dickins RA;Kogan SC;Shroyer KR;Sordella R;Hannon GJ;Lowe SW
通讯作者：
Lowe SW
影响因子：
27.4
作者：
Voulgarelis, M;Kokori, SIG;Moutsopoulos, HM
通讯作者：
Moutsopoulos, HM