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内源性促红细胞生成素具有免疫调节功能，可以限制小鼠自身免疫性肾病的表达。

Endogenous erythropoietin has immunoregulatory functions that limit the expression of autoimmune kidney disease in mice.

机构信息

Precision Immunology Institute, Translational Transplant Research Center, Icahn School of Medicine at Mount Sinai, New York, NY, United States.

Nephrology, Dialysis and Renal Transplant Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.

出版信息

Front Immunol. 2023 Jul 13;14:1195662. doi: 10.3389/fimmu.2023.1195662. eCollection 2023.

DOI:10.3389/fimmu.2023.1195662
PMID:37520571
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10381939/
Abstract

BACKGROUND

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 has not been previously evaluated.

METHODS

We generated mice in which we could downregulate EPO production using a doxycycline (DOX)-inducible, EPO-specific silencing RNA (shEPOrtTA), and we crossed them with B6.MRL-Fas/J mice that develop spontaneous lupus. We treated these B6.MRL/lpr shEPOrtTA 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 shEPOrtTA and in congenic shEPOrtTA controls.

RESULTS

In B6.MRL/lpr mice, 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.

DISCUSSION

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.

摘要

背景

重组促红细胞生成素（EPO）是一种具有促红细胞生成功能的肾脏产生的激素，已在小鼠和人类中显示出多种免疫调节作用，但生理水平的 EPO 是否调节免疫功能尚未得到评估。

方法

我们生成了可以使用强力霉素（DOX）诱导的、EPO 特异性沉默 RNA（shEPOrtTA）下调 EPO 产生的小鼠，并将其与自发发生狼疮的 B6.MRL-Fas/J 小鼠进行杂交。我们用 DOX 处理这些 B6.MRL/lpr shEPOrtTA，并在 6 个月大时通过流式细胞术分析免疫亚群，连续测量抗 dsDNA 抗体，并评估 B6.MRL/lpr shEPOrtTA 和同基因 shEPOrtTA 对照的疾病活动的临床体征。

结果

在 B6.MRL/lpr 小鼠中，下调增加了抗 dsDNA 自身抗体水平，并增加了疾病严重程度和生发中心 B 细胞的比例，与对照组相比。它还增加了巨噬细胞中 IL-6 和 MCP-1 的细胞内水平。

讨论

我们在狼疮的小鼠模型中的数据表明，内源性 EPO 可减少 T 细胞和 B 细胞的激活和自身抗体的产生，这支持了 EPO 作为一种生理性的负反馈机制来控制免疫稳态的结论。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3f1/10381939/eb356bfe12d7/fimmu-14-1195662-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3f1/10381939/f94f2946b6a2/fimmu-14-1195662-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3f1/10381939/6d67990a1f98/fimmu-14-1195662-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3f1/10381939/d0e93f9943cf/fimmu-14-1195662-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3f1/10381939/e3bb49217e45/fimmu-14-1195662-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3f1/10381939/eb356bfe12d7/fimmu-14-1195662-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3f1/10381939/f94f2946b6a2/fimmu-14-1195662-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3f1/10381939/6d67990a1f98/fimmu-14-1195662-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3f1/10381939/d0e93f9943cf/fimmu-14-1195662-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3f1/10381939/e3bb49217e45/fimmu-14-1195662-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3f1/10381939/eb356bfe12d7/fimmu-14-1195662-g005.jpg

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