转录因子IRF4功能障碍影响原发性免疫性血小板减少症患者Treg细胞的免疫抑制功能。

PubMed ID
发表日期 2019年月

原始出处 国际生物医学研究所
BioMed research international
作者 Tang  Meiwen  Cheng  Luya  Li  Feng  Wu  Boting  Chen  Pu  Zhan  Yanxia  Hua  Fanli  Min  Zhihui  Ke  Yang  Liu  Chanjuan  Yuan  Ling  Sun  Lihua  Chen  Hao  Ji  Lili  Cheng  Yunfeng 

文献标题 转录因子IRF4功能障碍影响原发性免疫性血小板减少症患者Treg细胞的免疫抑制功能。
Transcription Factor IRF4 Dysfunction Affects the Immunosuppressive Function of Treg Cells in Patients with Primary Immune Thrombocytopenia.

文献摘要 Background

ITP患者Th17/Treg平衡向Th17倾斜。IRF4与Treg细胞的免疫抑制功能及CD4+T细胞中IL-17的合成密切相关。本研究旨在探讨IRF4对ITP患者Th17/Treg细胞的影响。

Methods

从初诊ITP患者外周血单个核细胞分离Treg和Teff细胞。流式细胞术检测CD4+CD25hiFoxp3+Treg细胞和CD3+CD4+IL-17+Th17细胞百分率。培养后收集树突状细胞上清进行IL-10浓度测定。测定Tregs的IRF4水平。Teffs单独培养或与Tregs共培养24h。收集上清进行IL-17浓度测定。芯片qPCR检测IRF4与Treg细胞IL-10基因的结合强度。用安捷伦海马XF96分析仪进行TEFF和Treg的代谢测定。

Results

ITP患者Tregs分泌IL-10减少。ITP患者Tregs中IRF4与IL-10dna的结合强度高于正常对照组和Teffs组。ITP患者Tregs中IRF4的表达明显低于健康对照组。irf4mrna沉默后,健康对照组Th17细胞百分率显著增加。ITP患者Treg和Teff细胞代谢异常。

Conclusion

新诊断ITP患者Th17/Treg细胞比例失调和Treg细胞功能紊乱至少部分是由IRF4功能紊乱引起的。其机制可能与IRF4对Treg和Teff细胞代谢的影响有关。


Background

Th17/Treg balance skews towards Th17 in ITP patient. IRF4 has been highlighted for its close relationship to the immunosuppressive function of Treg cells and the IL-17 synthesis in CD4+ T cells. This study was aimed at examining the effects of IRF4 to the Th17/Treg cells in patients with ITP.

Methods

Treg and Teff cells were isolated from PBMCs of newly diagnosed ITP patients. The percentages of CD4+CD25hiFoxp3+Treg cells and the CD3+CD4+IL-17+Th17 cells were detected by flow cytometry. After being cultured, the supernatants of Tregs were collected for IL-10 concentration test. The IRF4 levels of Tregs were measured. Teffs were cultured alone or with Tregs for 24 hours. Then the supernatants were collected for IL-17 concentration test. The binding intensity of IRF4 to the gene IL-10 in Treg cells was detected by ChIP-qPCR. Metabolic assays for Teffs and Tregs were performed with Agilent Seahorse XF96 Analyzer.

Results

The secretion of IL-10 by Tregs was decreased in ITP patients. The intensity of IRF4 binding to IL-10 DNA of Tregs in patients was higher than that of normal controls and Teffs in ITP patients. The expressions of IRF4 of Tregs in ITP patients were remarkably lower than that of healthy controls. The percentage of Th17 cells in healthy controls was significantly increased after IRF4 mRNA silencing. Abnormal metabolism of Treg and Teff cells was found in ITP patients.

Conclusion

The skewed ratio of Th17/Treg cells and dysfunction of Treg cells in newly diagnosed ITP patients was at least partly caused by IRF4 dysfunction. The underlying mechanism might be the impact of IRF4 on the metabolism of Treg and Teff cells.


获取全文 10.1155/2019/1050285