Ming Yang, Ping Yi, Jiao Jiang, Ming Zhao, Haijing Wu, Qianjin Lu
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引用次数: 3
摘要
在适应性免疫中,B细胞在抗原呈递、抗体产生和促/抗炎细胞因子分泌中起着至关重要的作用。转录因子、细胞因子等多种翻译因子在表观遗传调控的配合下参与B细胞发育的调控。自身免疫性疾病通常以自身反应性B细胞和高致病性自身抗体为特征。B细胞耗竭疗法在小鼠模型和临床试验中的成功证明了B细胞在自身免疫性疾病发病机制中的作用。免疫检查点B细胞耐受失败导致自身反应性naïve B (BN)细胞积累,B细胞受体信号异常,B细胞反应失调,导致自身抗体介导的自身免疫反应。翻译因子的失调和B细胞的表观遗传改变已被证明与自身免疫性疾病(如系统性红斑狼疮、类风湿关节炎、原发性Sjögren综合征、多发性硬化症、糖尿病和天疱疮)中异常的B细胞室相关。本文就B细胞发育分化过程中翻译因子与表观遗传调控的相互作用及其在自身免疫性疾病发病中的作用机制进行综述。
Dysregulated translational factors and epigenetic regulations orchestrate in B cells contributing to autoimmune diseases.
B cells play a crucial role in antigen presentation, antibody production and pro-/anti-inflammatory cytokine secretion in adaptive immunity. Several translational factors including transcription factors and cytokines participate in the regulation of B cell development, with the cooperation of epigenetic regulations. Autoimmune diseases are generally characterized with autoreactive B cells and high-level pathogenic autoantibodies. The success of B cell depletion therapy in mouse model and clinical trials has proven the role of B cells in pathogenesis of autoimmune diseases. The failure of B cell tolerance in immune checkpoints results in accumulated autoreactive naïve B (BN) cells with aberrant B cell receptor signaling and dysregulated B cell response, contributing to self-antibody-mediated autoimmune reaction. Dysregulation of translational factors and epigenetic alterations in B cells has been demonstrated to correlate with aberrant B cell compartment in autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis, primary Sjögren's syndrome, multiple sclerosis, diabetes mellitus and pemphigus. This review is intended to summarize the interaction of translational factors and epigenetic regulations that are involved with development and differentiation of B cells, and the mechanism of dysregulation in the pathogenesis of autoimmune diseases.
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).