Reverse Regulation of Th1 and Treg Immune Responses by P2X7 Receptor: A Possible Cause of the Progression of Experimental Autoimmune Uveitis.

IF 2 4区 医学 Q3 OPHTHALMOLOGY
Yahui Cao, Xiaoxiang Peng, Shuping Luo, Yanan Du, Ronglan Zhao
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引用次数: 0

Abstract

Purpose: To study the regulatory effects and mechanisms of P2X7 receptors(P2X7R) on CD4+ regulatory T cells (Tregs) and pathogenic CD4+ T effector cells (Th1 cells).

Methods: In this research, an experimental autoimmune uveitis (EAU) mouse model was established to investigate the impact of P2X7R on Th1 and Treg immune responses.

Results: During the initial stage of EAU, appropriate activation of P2X7R leads to an enhanced Th1 immune response, including an increased proportion of CD4+ IFN-γ+ Th1 cells, increased production of cytokines tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ), and upregulation of transcription factor T-bet expression. Conversely, activation of P2X7R resulted in inhibition of Treg immune response, including a reduced proportion of CD4+Foxp3+Tregs, a decreased in cytokines transforming growth factor-beta (TGF-β) and interleukin-10 (IL-10), and a downregulation of the transcription factor Foxp3 expression. Extracellular signal-regulated kinase 1/2 (ERK1/2) signal and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) may be related to these effects. Interestingly, we observed that both Th1 and Tregs immune responses were reduced in P2rx-/- mice compared with P2rx7+/+ mice.

Conclusions: Our findings indicate that the promoting role of P2X7R in the early pathogenesis of EAU may be related to the contrary regulation of Th1 cells and Tregs, providing a new theoretical basis for the development of P2X7R targeted therapy.

P2X7受体对Th1和Treg免疫应答的反向调控:实验性自身免疫性葡萄膜炎进展的可能原因
目的:研究P2X7受体(P2X7R)对CD4+调节性T细胞(Tregs)和致病性CD4+ T效应细胞(Th1细胞)的调控作用及其机制。方法:本研究建立实验性自身免疫性葡萄膜炎(EAU)小鼠模型,探讨P2X7R对Th1和Treg免疫应答的影响。结果:在EAU的初始阶段,P2X7R的适当激活导致Th1免疫应答增强,包括CD4+ IFN-γ+ Th1细胞比例增加,细胞因子肿瘤坏死因子-α (TNF-α)和干扰素-γ (IFN-γ)的产生增加,转录因子T-bet表达上调。相反,P2X7R的激活导致Treg免疫反应的抑制,包括CD4+Foxp3+Treg的比例降低,细胞因子转化生长因子-β (TGF-β)和白细胞介素-10 (IL-10)的降低,转录因子Foxp3的表达下调。细胞外信号调节激酶1/2 (ERK1/2)信号和活化B细胞的核因子κB轻链增强子(NF-κB)可能与这些作用有关。有趣的是,我们观察到,与P2rx7+/+小鼠相比,P2rx-/-小鼠的Th1和Tregs免疫反应都降低了。结论:我们的研究结果提示P2X7R在EAU早期发病中的促进作用可能与Th1细胞和Tregs的反向调控有关,为开发P2X7R靶向治疗提供了新的理论依据。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Current Eye Research
Current Eye Research 医学-眼科学
CiteScore
4.60
自引率
0.00%
发文量
163
审稿时长
12 months
期刊介绍: The principal aim of Current Eye Research is to provide rapid publication of full papers, short communications and mini-reviews, all high quality. Current Eye Research publishes articles encompassing all the areas of eye research. Subject areas include the following: clinical research, anatomy, physiology, biophysics, biochemistry, pharmacology, developmental biology, microbiology and immunology.
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