Department of Internal Medicine, Rheumatic Diseases Division and Department of Immunology, UT Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX, 75390-8884, USA.
Curr Rheumatol Rep. 2021 Nov 24;23(11):80. doi: 10.1007/s11926-021-01047-1.
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.
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.
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。
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。
