Ilenia Cammarata , Valeria Pinna , Ilenia Pacella , Ivano Rotella , Annarosa Soresina , Raffaele Badolato , Alessandro Plebani , Claudio Pignata , Emilia Cirillo , Anna Maria Zicari , Francesco Violi , Roberto Carnevale , Lorenzo Loffredo , Silvia Piconese
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To this aim, the frequency of Tregs was analysed through intracellular flow cytometry in a cohort of adult X-CGD patients, carriers and controls. We found that Tregs were significantly expanded and activated in blood of adult X-CGD patients, and this was associated with activation of conventional CD4<sup>+</sup> <em>T</em> cells (Tconvs). T cell activation was characterised by accumulation of intracellular ROS, not derived from NOX2 but likely produced by cellular metabolism. The higher TNF production by Tconvs in X-CGD patients might contribute to the expansion of Tregs through the TNFR2 receptor. 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引用次数: 0
摘要
X 连锁慢性肉芽肿病(X-CGD)是一种以反复感染为特征的罕见遗传病,由 NOX2 基因突变引起。相当一部分 X-CGD 患者表现出免疫失调的症状。调节性 T 细胞(Tregs)是一种 CD4+ T 淋巴细胞,能在炎症活跃时扩增并预防自身免疫性疾病。在此,我们想知道 X-CGD 是否与成年患者的 Treg 功能障碍有关。为此,我们通过细胞内流式细胞术分析了一组 X-CGD 成年患者、携带者和对照组中 Treg 的频率。我们发现,在成年 X-CGD 患者的血液中,Tregs 明显增殖和活化,这与常规 CD4+ T 细胞(Tconvs)的活化有关。T细胞活化的特点是细胞内ROS的积累,这些ROS并非来自NOX2,而可能是由细胞代谢产生的。X-CGD患者的Tconvs产生的TNF较高,这可能有助于Tregs通过TNFR2受体扩增。总之,我们的数据表明,成人 X-CGD 中的 Tregs 会随着免疫激活而扩增,而 NOX2 依赖性 ROS 含量的增加是活化 T 细胞的一个特征。
In adult X-CGD patients, regulatory T cells are expanded while activated T cells display a NOX2-independent ROS increase
The X-linked chronic granulomatous disease (X-CGD), a rare genetic disease characterised by recurrent infections, is caused by mutations of NOX2. Significant proportions of X-CGD patients display signs of immune dysregulation. Regulatory T cells (Tregs) are CD4+T lymphocytes that expand in active inflammation and prevent autoimmune disorders. Here we asked whether X-CGD is associated to Treg dysfunctions in adult patients. To this aim, the frequency of Tregs was analysed through intracellular flow cytometry in a cohort of adult X-CGD patients, carriers and controls. We found that Tregs were significantly expanded and activated in blood of adult X-CGD patients, and this was associated with activation of conventional CD4+T cells (Tconvs). T cell activation was characterised by accumulation of intracellular ROS, not derived from NOX2 but likely produced by cellular metabolism. The higher TNF production by Tconvs in X-CGD patients might contribute to the expansion of Tregs through the TNFR2 receptor. In summary, our data indicate that Tregs expand in adult X-CGD in response to immune activation, and that the increase of NOX2-independent ROS content is a feature of activated T cells.
期刊介绍:
Immunology Letters provides a vehicle for the speedy publication of experimental papers, (mini)Reviews and Letters to the Editor addressing all aspects of molecular and cellular immunology. The essential criteria for publication will be clarity, experimental soundness and novelty. Results contradictory to current accepted thinking or ideas divergent from actual dogmas will be considered for publication provided that they are based on solid experimental findings.
Preference will be given to papers of immediate importance to other investigators, either by their experimental data, new ideas or new methodology. Scientific correspondence to the Editor-in-Chief related to the published papers may also be accepted provided that they are short and scientifically relevant to the papers mentioned, in order to provide a continuing forum for discussion.