STAT4 和 STAT6,它们在细胞和体液免疫以及各种人类疾病中的作用。

IF 4.3 4区 医学 Q2 IMMUNOLOGY
International Reviews of Immunology Pub Date : 2024-01-01 Epub Date: 2024-08-26 DOI:10.1080/08830185.2024.2395274
Manlio Tolomeo, Antonio Cascio
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引用次数: 0

摘要

信号转导和激活转录(STAT)4 和 STAT6 在免疫细胞中发挥着至关重要的作用,它们从特定的细胞因子受体转导信号,并诱导参与细胞介导免疫和体液免疫的基因转录。这两种针对病原体的不同防御机制是由两种被称为 Th1 和 Th2 细胞的特定 CD4+ T 辅助(Th)细胞调控的。许多研究表明,包括癌症、炎症性疾病、自身免疫性疾病和过敏性疾病在内的多种疾病都与 Th1/Th2 失衡有关,而这种失衡是由 STAT4 或 STAT6 的表达/活性增高或降低(通常是由于遗传和表观遗传失常造成的)引起的。在不同的肿瘤和自身免疫性疾病中观察到 STAT4 表达的改变,而在过敏性疾病(如特应性皮炎、过敏性哮喘、食物过敏)和肿瘤(如霍奇金淋巴瘤和非霍奇金淋巴瘤)中经常观察到 STAT6 信号通路的失调。最近,在SARS-CoV2和猴痘感染中观察到STAT4和STAT6表达失调,这两种疾病在许多国家仍是突发公共卫生事件。SARS-CoV-2 可诱导 Th1 和 Th2 反应失衡,STAT6 在肺炎细胞的细胞膜和细胞核中被激活,从而推动 Th2 极化和细胞因子风暴。在猴痘感染中,病毒可通过诱导 Th2 反应促进免疫逃避,而 Th2 反应反过来又会抑制消除病毒所必需的 Th1 反应。此外,STAT4 基因变异会增加患系统性红斑狼疮的风险,这种变异似乎在抵御 SARS-CoV-2 感染方面发挥了作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
STAT4 and STAT6, their role in cellular and humoral immunity and in diverse human diseases.

Signal transducer and activator of transcription (STAT) 4 and STAT6 play a crucial role in immune cells by transducing signals from specific cytokine receptors, and inducing transcription of genes involved in cell-mediated and humoral immunity. These two different defense mechanisms against pathogens are regulated by two specific CD4+ T helper (Th) cells known as Th1 and Th2 cells. Many studies have shown that several diseases including cancer, inflammatory, autoimmune and allergic diseases are associated with a Th1/Th2 imbalance caused by increased or decreased expression/activity of STAT4 or STAT6 often due to genetic and epigenetic aberrances. An altered expression of STAT4 has been observed in different tumors and autoimmune diseases, while a dysregulation of STAT6 signaling pathway is frequently observed in allergic conditions, such as atopic dermatitis, allergic asthma, food allergy, and tumors such as Hodgkin and non-Hodgkin lymphomas. Recently, dysregulations of STAT4 and STAT6 expression have been observed in SARS-CoV2 and monkeypox infections, which are still public health emergencies in many countries. SARS-CoV-2 can induce an imbalance in Th1 and Th2 responses with a predominant activation of STAT6 in the cytosol and nuclei of pneumocytes that drives Th2 polarization and cytokine storm. In monkeypox infection the virus can promote an immune evasion by inducing a Th2 response that in turn inhibits the Th1 response essential for virus elimination. Furthermore, genetic variations of STAT4 that are associated with an increased risk of developing systemic lupus erythematosus seem to play a role in defense against SARS-CoV-2 infection.

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来源期刊
CiteScore
11.00
自引率
4.00%
发文量
24
期刊介绍: This review journal provides the most current information on basic and translational research in immunology and related fields. In addition to invited reviews, the journal accepts for publication articles and editorials on relevant topics proposed by contributors. Each issue of International Reviews of Immunology contains both solicited and unsolicited review articles, editorials, and ''In-this-Issue'' highlights. The journal also hosts reviews that position the authors'' original work relative to advances in a given field, bridging the gap between annual reviews and the original research articles. This review series is relevant to all immunologists, molecular biologists, microbiologists, translational scientists, industry researchers, and physicians who work in basic and clinical immunology, inflammatory and allergic diseases, vaccines, and additional topics relevant to medical research and drug development that connect immunology to disciplines such as oncology, cardiovascular disease, and metabolic disorders. Covered in International Reviews of Immunology: Basic and developmental immunology (innate and adaptive immunity; inflammation; and tumor and microbial immunology); Clinical research (mechanisms of disease in man pertaining to infectious diseases, autoimmunity, allergy, oncology / immunology); and Translational research (relevant to biomarkers, diagnostics, vaccines, and drug development).
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