TANK is a negative regulator of Toll-like receptor signaling and is critical for the prevention of autoimmune nephritis.
TANK is a negative regulator of Toll-like receptor signaling and is critical for the prevention of autoimmune nephritis.
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免疫反应的强度和持续时间由多种调节Toll样受体(TLR)信号的蛋白质控制。TRAF家族成员相关的NF-κB激活物(TANK)参与了干扰素调节因子-3和NF-κB的正向调节。我们证明TRAF不参与干扰素反应，而是TLR信号诱导的促炎细胞因子产生的负性调节因子。在Tank−/−巨噬细胞中，TLR诱导的TRAF6多泛素化水平上调。值得注意的是，Tank−/−小鼠由于免疫复合体的沉积而自发地发展为致命性肾小球肾炎。通过抗生素治疗或不使用白介素6或MyD88可挽救Tank−/−小鼠体内自身抗体的产生。这些结果表明，TANK抑制了肠道共生微生物组成的TLR信号转导。
The intensity and duration of immune responses are controlled by multiple proteins that modulate Toll-like receptor (TLR) signaling. TRAF family member-associated NF-κB activator (TANK) has been implicated in positive regulation of interferon-regulatory factor-3 as well as NF-κB. Here we demonstrate that TANK is not involved in interferon responses, and is a negative regulator of proinflammatory cytokine production induced by TLR signaling. TLR-induced polyubiquitination of TRAF6 was upregulated in Tank−/−macrophages. Notably, Tank−/− mice spontaneously developed fatal glomerulonephritis owing to deposition of immune complexes. Autoantibody production in Tank−/− mice was rescued by antibiotic treatment or the absence of interleukin (IL)-6 or MyD88. These results demonstrate that constitutive TLR signaling by intestinal commensal microflora is suppressed by TANK.
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