Regulation of SETD2 maintains immune regulatory function in macrophages to suppress airway allergy

IF 4.9 3区 医学 Q2 IMMUNOLOGY
Immunology Pub Date : 2024-06-10 DOI:10.1111/imm.13823
Lei Zhang, Junyi Wang, Xiaoyu Liu, Xiaojun Xiao, Yu Liu, Qinmiao Huang, Jing Li, Guoping Li, Pingchang Yang
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Abstract

SET domain-containing 2 (SETD2) is a histone methyltransferase. It regulates the activity of H3K36me3 to enhance gene transcription. Macrophages (Mϕs) are one of the cell types involved in immune response. The purpose of this study is to clarify the role of SETD2 in regulating the immune property of Mϕ. The Mφs were isolated from the bronchoalveolar lavage fluid (BALF) and analysed through flow cytometry and RNA sequencing. A mouse strain carrying Mφs deficient in SETD2 was used. A mouse model of airway allergy was established with the ovalbumin/alum protocol. Less expression of SETD2 was observed in airway Mϕs in patients with allergic asthma. SETD2 of M2 cells was associated with the asthmatic clinical response. Sensitization reduced the expression of SETD2 in mouse respiratory tract M2 cells, which is associated with the allergic reaction. Depletion of SETD2 in Mφs resulted in Th2 pattern inflammation in the lungs. SETD2 maintained the immune regulatory ability in airway M2 cells. SETD2 plays an important role in the maintenance of immune regulatory property of airway Mφs.

Abstract Image

调节 SETD2 可维持巨噬细胞的免疫调节功能,从而抑制气道过敏。
含 SET 结构域的 2(SETD2)是一种组蛋白甲基转移酶。它能调节 H3K36me3 的活性,从而增强基因转录。巨噬细胞(Mϕs)是参与免疫反应的细胞类型之一。本研究旨在阐明 SETD2 在调节 Mϕ 免疫特性中的作用。研究人员从支气管肺泡灌洗液(BALF)中分离出 Mφs,并通过流式细胞术和 RNA 测序对其进行分析。使用了携带 SETD2 缺失的 Mφs 的小鼠品系。用卵清蛋白/明矾方案建立了气道过敏小鼠模型。在过敏性哮喘患者的气道 Mϕs 中观察到较少的 SETD2 表达。M2 细胞的 SETD2 与哮喘的临床反应有关。致敏减少了小鼠呼吸道 M2 细胞中 SETD2 的表达,而这与过敏反应有关。Mφ中SETD2的消耗导致肺部Th2模式炎症。SETD2 可维持气道 M2 细胞的免疫调节能力。SETD2 在维持气道 Mφs 的免疫调节特性中发挥了重要作用。
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来源期刊
Immunology
Immunology 医学-免疫学
CiteScore
11.90
自引率
1.60%
发文量
175
审稿时长
4-8 weeks
期刊介绍: Immunology is one of the longest-established immunology journals and is recognised as one of the leading journals in its field. We have global representation in authors, editors and reviewers. Immunology publishes papers describing original findings in all areas of cellular and molecular immunology. High-quality original articles describing mechanistic insights into fundamental aspects of the immune system are welcome. Topics of interest to the journal include: immune cell development, cancer immunology, systems immunology/omics and informatics, inflammation, immunometabolism, immunology of infection, microbiota and immunity, mucosal immunology, and neuroimmunology. The journal also publishes commissioned review articles on subjects of topical interest to immunologists, and commissions in-depth review series: themed sets of review articles which take a 360° view of select topics at the heart of immunological research.
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