TLR7 信号在狼疮 B 细胞中的作用：协同因子和下游信号的新见解。
TLR7 Signaling in Lupus B Cells: New Insights into Synergizing Factors and Downstream Signals.
机构信息
Department of Internal Medicine, Rheumatic Diseases Division and Department of Immunology, UT Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX, 75390-8884, USA.
出版信息
Curr Rheumatol Rep. 2021 Nov 24;23(11):80. doi: 10.1007/s11926-021-01047-1.
PURPOSE OF THE REVIEW
Systemic lupus erythematosus (SLE) is driven by nucleic acid-containing antigens that stimulate endosomal TLRs. We review new advances in our understanding of how TLR7 signaling in B cells drives autoimmunity.
RECENT FINDINGS
Pathogenic B cell responses to TLR7 engagement are shaped by the disease-associated cytokine environment. TLR7, IFNγ, and IL-21 together promote the formation of autoreactive germinal centers and the ABC/DN2 B cell subset. BAFF and type 1 IFNs enhance autoantibody production from transitional B cells in concert with TLR7. TLR7 signaling components STAT1, BANK1, IRF5, SLC15A4, and CXorf21/TASL are associated genetically with SLE and important for lupus development in mice, while role of T-bet is controversial. Proper control of TLR7 trafficking by UNC93B1, syntenin-1, and αvβ3 integrin is critical for preventing autoimmunity. A better understanding of TLR7 signaling has revealed potential new therapeutic approaches for SLE, several of which are being tested in animal models or clinical trials.
目的综述
系统性红斑狼疮（SLE）是由含有核酸的抗原驱动的，这些抗原能刺激内体 TLR。我们综述了关于 TLR7 在 B 细胞中信号转导如何驱动自身免疫的新进展。
最新发现
TLR7 与疾病相关细胞因子环境共同影响致病性 B 细胞的反应。TLR7、IFNγ 和 IL-21 共同促进自身反应性生发中心和 ABC/DN2 B 细胞亚群的形成。BAFF 和 I 型 IFNs 与 TLR7 协同作用增强了过渡 B 细胞的自身抗体产生。TLR7 信号转导成分 STAT1、BANK1、IRF5、SLC15A4 和 CXorf21/TASL 在遗传上与 SLE 相关，并且对小鼠狼疮的发展很重要，而 T-bet 的作用则存在争议。UNC93B1、衔接蛋白-1 和 αvβ3 整合素对 TLR7 转运的适当控制对于预防自身免疫至关重要。对 TLR7 信号转导的更好理解揭示了 SLE 的潜在新治疗方法，其中一些正在动物模型或临床试验中进行测试。
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