TLR8 deficiency leads to autoimmunity in mice
TLR8 deficiency leads to autoimmunity in mice
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DOI：
10.1172/jci42081
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发表时间：
2010-10-01
影响因子：
15.9
通讯作者：
Alexopoulou, Lena
中科院分区：
文献类型：
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作者：
Demaria, Olivier;Pagni, Philippe P.;Alexopoulou, Lena
tlr通过检测微生物的保守分子产物在诱导免疫应答中发挥重要作用。然而，TLR8的功能在很大程度上是未知的。在本研究中，我们研究了TLR8信号在小鼠免疫中的作用。我们发现Tlr8(-/-) dc过表达TLR7，对各种TLR7配体有高反应，TLR7配体R848刺激后NF-kappa B激活更强、更快。Tlr8（-/-）小鼠表现为脾肿大，边缘带（MZ）和B1 B细胞发育缺陷，血清IgM和IgG2a水平升高。此外，Tlr8（-/-）小鼠表现出针对小核糖核蛋白、核糖核蛋白和dsDNA的血清自身抗体水平升高，并发生肾小球肾炎，而Tlr7（-/-）和Tlr8(-1-)Tlr7（-/-）小鼠均未表现出Tlr8（-/-）小鼠所观察到的任何表型。这些数据为小鼠TLR8在调节小鼠TLR7表达和预防自发自身免疫中发挥关键作用提供了证据。
TLRs play an essential role in the induction of immune responses by detecting conserved molecular products of microorganisms. However, the function of TLR8 is largely unknown. In the current study, we investigated the role of TLR8 signaling in immunity in mice. We found that Tlr8(-/-) DCs overexpressed TLR7, were hyperresponsive to various TLR7 ligands, and showed stronger and faster NF-kappa B activation upon stimulation with the TLR7 ligand R848. Tlr8(-/-) mice showed splenomegaly, defective development of marginal zone (MZ) and B1 B cells, and increased serum levels of IgM and IgG2a. Furthermore, Tlr8(-/-) mice exhibited increased serum levels of autoantibodies against small nuclear ribonucleoproteins, ribonucleoprotein, and dsDNA and developed glomerulonephritis, whereas neither Tlr7(-/-) nor Tlr8(-1-)Tlr7(-/-) mice showed any of the phenotypes observed in Tlr8(-/-) mice. These data provide evidence for a pivotal role for mouse TLR8 in the regulation of mouse TLR7 expression and prevention of spontaneous autoimmunity.