源自真菌和细菌的微生物相关分子模式可促进 1 型自身免疫性胰腺炎患者产生 IgG4 抗体。

IF 3.7 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Cytokine Pub Date : 2024-09-05 DOI:10.1016/j.cyto.2024.156748
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引用次数: 0

摘要

IgG4 抗体(Ab)反应增强是 1 型自身免疫性胰腺炎(AIP)的一个显著特征。与 IgG4 抗体产生相关的先天性免疫反应尚不明确。我们以前曾报道过,从 1 型自身免疫性胰腺炎患者体内分离出的外周血单核细胞(PBMCs)在受到细菌细胞壁成分刺激后会产生大量 IgG4 Ab。此外,我们还发现,质体树突状细胞在感受到肠道细菌后会被激活,产生干扰素(IFN)-α、白细胞介素(IL)-33 和 B 细胞活化因子(BAFF),从而介导实验性 AIP 的发生。在本研究中,我们试图阐明针对真菌的先天性免疫在诱导 1 型 AIP 中 IgG4 Ab 反应增强中的作用。我们用多种细菌和真菌细胞壁成分刺激从健康对照组和 1 型 AIP 患者体内分离出的 PBMC。使用酶联免疫吸附试验测定了 IgG1、IgG4 和细胞因子的浓度。从细菌和真菌中提取的细胞壁成分可诱导1型AIP患者产生IgG1和IgG4抗体。与健康对照组的有限分子模式相比,各种类型的微生物相关分子模式会增强 1 型 AIP 患者 IgG4 Ab 的产生。细菌和真菌细胞壁成分导致的 IgG1 和 IgG4 Ab 生成增强与 IFN-α、IFN-γ、IL-10、IL-33 和 BAFF 的作用平行。总之,真菌和细菌的细胞壁成分可促进 1 型 AIP 患者的 IgG4 Ab 反应。
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Microbe-associated molecular patterns derived from fungi and bacteria promote IgG4 antibody production in patients with type 1 autoimmune pancreatitis

Enhanced IgG4 antibody (Ab) response is a prominent feature of type 1 autoimmune pancreatitis (AIP). Innate immune responses associated with IgG4 Ab production are poorly defined. We have previously reported that peripheral blood mononuclear cells (PBMCs) isolated from patients with type 1 AIP produce large amounts of IgG4 Abs upon stimulation with bacterial cell wall components. In addition, we showed that activation of plasmacytoid dendritic cells producing interferon (IFN)-α, interleukin (IL)-33, and B cell-activating factor (BAFF) upon sensing intestinal bacteria mediates the development of experimental AIP. In this study, we attempted to clarify the role of innate immunity against fungi in inducing enhanced IgG4 Ab responses in type 1 AIP. PBMCs isolated from healthy controls and patients with type 1 AIP were stimulated with a broad range of bacterial and fungal cell wall components. The concentrations of IgG1, IgG4, and cytokines were measured using enzyme-linked immunosorbent assays. Cell wall components derived from bacteria and fungi induced IgG1 and IgG4 Ab production in patients with type 1 AIP. Various types of microbe-associated molecular pattern motifs enhanced IgG4 Ab production in patients with type 1 AIP compared with the limited motifs in healthy controls. The enhanced IgG1 and IgG4 Ab production that followed in response to bacterial and fungal cell wall components was parallel to that of IFN-α, IFN-γ, IL-10, IL-33, and BAFF. In conclusion, cell wall components derived from fungi as well as bacteria promote IgG4 Ab responses in patients with type 1 AIP.

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来源期刊
Cytokine
Cytokine 医学-免疫学
CiteScore
7.60
自引率
2.60%
发文量
262
审稿时长
48 days
期刊介绍: The journal Cytokine has an open access mirror journal Cytokine: X, sharing the same aims and scope, editorial team, submission system and rigorous peer review. * Devoted exclusively to the study of the molecular biology, genetics, biochemistry, immunology, genome-wide association studies, pathobiology, diagnostic and clinical applications of all known interleukins, hematopoietic factors, growth factors, cytotoxins, interferons, new cytokines, and chemokines, Cytokine provides comprehensive coverage of cytokines and their mechanisms of actions, 12 times a year by publishing original high quality refereed scientific papers from prominent investigators in both the academic and industrial sectors. We will publish 3 major types of manuscripts: 1) Original manuscripts describing research results. 2) Basic and clinical reviews describing cytokine actions and regulation. 3) Short commentaries/perspectives on recently published aspects of cytokines, pathogenesis and clinical results.
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