Toll-like receptor signalling in B cells during systemic lupus erythematosus.
Toll-like receptor signalling in B cells during systemic lupus erythematosus.
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全身性红斑狼疮期间，B细胞中的Toll样受体信号传导。
DOI：
10.1038/s41584-020-00544-4
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发表时间：
2021-03
期刊：
影响因子：
--
通讯作者：
Dörner T
中科院分区：
文献类型：
--
作者：
Fillatreau S;Manfroi B;Dörner T
B淋巴细胞在自身免疫性疾病中具有中心作用，自身免疫性疾病通常由特异性自身抗体模式定义并且以B细胞耐受性丧失为特征。与B细胞过度活跃相关的典型疾病是系统性红斑狼疮（SLE）。在SLE患者中，B细胞对自身抗原耐受性的丧失由Toll样受体（TLR）以细胞内在方式控制，Toll样受体（TLR）感测核内体中的核酸。TLR 7驱动参与自身抗体产生和疾病发病机制的滤泡外B细胞应答和生发中心反应。令人惊讶的是，TLR 9似乎对SLE有保护作用，尽管它是产生识别双链DNA相关抗原的自身抗体所必需的，双链DNA相关抗原在SLE中丰富并且是这种疾病的标志。TLR 9的保护功能至少部分由其限制TLR 7的刺激活性的能力介导。TLR 7和TLR 9在狼疮样疾病和SLE患者中的B细胞的效应子功能中的作用，以及B细胞中TLR信号传导的独特特征，表明靶向SLE中的TLR信号传导可能是治疗有益的。系统性红斑狼疮（SLE）中B细胞对自身抗原耐受性的丧失是由TLR 7驱动的，而TLR 9似乎通过限制TLR 7的刺激活性来保护免受SLE。B细胞中Toll样受体信号传导的独特特征暗示其为SLE的治疗靶点。B细胞中的内源性TLR 7和TLR 9信号转导在系统性红斑狼疮（SLE）的发生和发病中起重要作用。在SLE患者中，效应浆细胞通过滤泡外反应和自发性生发中心的形成产生。TLR 7在卵泡外反应和生发中心介导的反应中起关键作用。一些浆细胞产生IL-10，在狼疮样疾病中具有保护作用。
B lymphocytes have a central role in autoimmune diseases, which are often defined by specific autoantibody patterns and feature a loss of B cell tolerance. A prototypic disease associated with B cell hyperactivity is systemic lupus erythematosus (SLE). In patients with SLE, the loss of B cell tolerance to autoantigens is controlled in a cell-intrinsic manner by Toll-like receptors (TLRs), which sense nucleic acids in endosomes. TLR7 drives the extrafollicular B cell response and the germinal centre reaction that are involved in autoantibody production and disease pathogenesis. Surprisingly, TLR9 seems to protect against SLE, even though it is required for the production of autoantibodies recognizing double-stranded DNA-associated antigens, which are abundant in SLE and are a hallmark of this disease. The protective function of TLR9 is at least partly mediated by its capacity to limit the stimulatory activity of TLR7. The roles of TLR7 and TLR9 in the effector function of B cells in lupus-like disease and in patients with SLE, and the unique features of TLR signalling in B cells, suggest that targeting TLR signalling in SLE might be therapeutically beneficial. Loss of B cell tolerance to autoantigens in systemic lupus erythematosus (SLE) is driven by TLR7, whereas TLR9 appears to protect against SLE by limiting the stimulatory activity of TLR7. The unique features of Toll-like receptor signalling in B cells implicate it as a therapeutic target in SLE. Intrinsic TLR7 and TLR9 signalling in B cells plays an important role in the development and pathogenesis of systemic lupus erythematosus (SLE). In patients with SLE, effector plasma cells are generated via the extrafollicular response and via the formation of spontaneous germinal centres. TLR7 plays key roles in the extrafollicular response and the response mediated by germinal centres. Some plasma cells produce IL-10 and can have protective roles in lupus-like disease.
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