The Roles of Monocytes and Macrophages in Behçet's Disease With Focus on M1 and M2 Polarization.
The Roles of Monocytes and Macrophages in Behçet's Disease With Focus on M1 and M2 Polarization.
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DOI：
10.3389/fimmu.2022.852297
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发表时间：
2022
影响因子：
7.3
通讯作者：
Nakajima H
中科院分区：
文献类型：
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作者：
Hirahara L;Takase-Minegishi K;Kirino Y;Iizuka-Iribe Y;Soejima Y;Yoshimi R;Nakajima H
BEHçet‘s病(BD)是一种全身性炎症性疾病，以反复发作的口腔溃疡、生殖器溃疡、皮肤炎和葡萄膜炎为特征。此外，其他可能危及生命的损害可能发生在肠道、血管和中枢神经系统。BD表型的这种异质性阻碍了靶向治疗策略的发展。BD的发病机制尚未完全阐明，但很可能是遗传易感人群对环境因素，如微生物组因素的反应而发展为BD。遗传分析已经确定了多种BD易感基因，这些易感基因在人类白细胞抗原呈递途径、Th1和Th17细胞以及与单核/巨噬细胞相关的自体炎症中发挥作用，或者增加促炎细胞因子的水平，降低抗炎细胞因子的水平，或者作用于功能障碍的粘膜屏障。我们的功能分析表明，通过IL-10损伤M2单核/巨噬细胞介导的抗炎功能是BD发病的关键。因此，我们认为BD是一种M1显性疾病。在这篇综述中，我们描述了单核细胞和巨噬细胞在BD中的作用，并考虑了这些细胞作为治疗靶点的潜力。
Behçet’s disease (BD) is a systemic inflammatory disease characterized by recurrent oral ulcers, genital ulcers, cutaneous inflammation, and uveitis. In addition, other potentially life-threatening lesions may occur in the intestinal tract, blood vessels, and central nervous system. This heterogeneity of the BD phenotype hampers development of a targeted treatment strategy. The pathogenesis of BD is not fully elucidated, but it is likely that genetically susceptible people develop BD in response to environmental factors, such as microbiome factors. Genetic analyses have identified various BD susceptibility loci that function in HLA-antigen presentation pathways, Th1 and Th17 cells, and autoinflammation related to monocytes/macrophages, or that increase levels of pro-inflammatory cytokines, reduce levels of anti-inflammatory cytokines, or act in dysfunctional mucous barriers. Our functional analyses have revealed that impairment of M2 monocyte/macrophage-mediated anti-inflammatory function through IL-10 is crucial to BD pathogenesis. We, therefore, propose that BD is an M1-dominant disease. In this review, we describe the roles of monocytes and macrophages in BD and consider the potential of these cells as therapeutic targets.
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