MZB1 介导的 IgA 分泌可抑制肠道炎症引发的结直肠癌的发展和恶化。

IF 7.9 2区 医学 Q1 IMMUNOLOGY Mucosal Immunology Pub Date : 2024-06-01 DOI:10.1016/j.mucimm.2023.12.002
Yue Tang , Xiaoqian Feng , Qing Lu , Chaoqun Cui , Meiping Yu , Zichao Wen , Yingying Luan , Lulu Dong , Ziying Hu , Runyun Zhang , Chunhui Lu , Jie Liu , Reiko Shinkura , Koji Hase , Ji-Yang Wang
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引用次数: 0

摘要

结肠直肠癌(CRC)在全球死亡原因中名列前茅。肠道炎症是诱发 CRC 的一个重要风险因素,因为患有炎症性肠病的患者会增加 CRC 的发病率。IgA 在维持肠道平衡和预防炎症方面的作用已得到公认。我们早前的研究表明,边缘区和 B1 细胞特异性蛋白(MZB1)能促进肠道 IgA 分泌,缺失该蛋白会导致明显的右旋糖酐硫酸钠盐(DSS)诱导的结肠炎。在本研究中,我们利用偶氮甲烷(AOM)/DSS诱导的结直肠癌模型探讨了MZB1在结直肠癌发展中的作用。与 Mzb1+/+ 小鼠相比,我们观察到 Mzb1-/- 小鼠肿瘤结节的数量和大小均有所增加。Mzb1-/-小鼠CRC发病和进展的增加与肠道IgA水平降低、肠道菌群改变以及更严重的肠道和全身炎症有关。口服单克隆 IgA W27 可减轻肠道炎症和 AOM/DSS 诱导的 CRC。值得注意的是,Mzb1+/+和Mzb1-/-小鼠从出生后第10天开始同群饲养会导致相似的CRC发展。我们的发现强调了 MZB1 介导的 IgA 分泌在抑制肠道炎症引发的 CRC 的发生和发展中的关键作用。此外,我们的研究还凸显了微生物群组成对肠道炎症的深远影响,而肠道 IgA 水平则可调节微生物群组成。尽管如此,要在结肠炎的严重程度和随后的 CRC 发展与特定微生物群的存在与否之间建立直接的相关性仍具有挑战性。
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MZB1-mediated IgA secretion suppresses the development and progression of colorectal cancer triggered by gut inflammation

Colorectal cancer (CRC) ranks among the top causes of mortality globally. Gut inflammation is one crucial risk factor that augments CRC development since patients suffering from inflammatory bowel disease have an increased incidence of CRC. The role of immunoglobulin (Ig)A in maintaining gut homeostasis and preventing inflammation has been well established. Our earlier work demonstrated that the marginal zone and B1 cell-specific protein (MZB1) promotes gut IgA secretion and its absence results in pronounced dextran sulfate sodium salt (DSS)-induced colitis. In the present study, we explored the role of MZB1 in CRC development using the azoxymethane (AOM)/DSS-induced CRC model. We observed an increase in both the number and size of the tumor nodules in Mzb1−/− mice compared with Mzb1+/+ mice. The increase in CRC development and progression in Mzb1−/− mice was associated with reduced intestinal IgA levels, altered gut flora, and more severe gut and systemic inflammation. Oral administration of the monoclonal IgA, W27, alleviated both the gut inflammation and AOM/DSS-induced CRC. Notably, cohousing Mzb1+/+ and Mzb1−/− mice from the 10th day after birth led to similar CRC development. Our findings underscore the pivotal role of MZB1-mediated IgA secretion in suppressing the onset and progression of CRC triggered by gut inflammation. Moreover, our study highlights the profound impact of microbiota composition, modulated by gut IgA levels, on gut inflammation. Nonetheless, establishing a direct correlation between the severity of colitis and subsequent CRC development and the presence or absence of a particular microbiota is challenging.

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来源期刊
Mucosal Immunology
Mucosal Immunology 医学-免疫学
CiteScore
16.60
自引率
3.80%
发文量
100
审稿时长
12 days
期刊介绍: Mucosal Immunology, the official publication of the Society of Mucosal Immunology (SMI), serves as a forum for both basic and clinical scientists to discuss immunity and inflammation involving mucosal tissues. It covers gastrointestinal, pulmonary, nasopharyngeal, oral, ocular, and genitourinary immunology through original research articles, scholarly reviews, commentaries, editorials, and letters. The journal gives equal consideration to basic, translational, and clinical studies and also serves as a primary communication channel for the SMI governing board and its members, featuring society news, meeting announcements, policy discussions, and job/training opportunities advertisements.
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