RNA-associated autoantigens activate B cells by combined B cell antigen receptor/Toll-like receptor 7 engagement.
RNA-associated autoantigens activate B cells by combined B cell antigen receptor/Toll-like receptor 7 engagement.
复制标题
DOI：
10.1084/jem.20050630
复制
发表时间：
2005-11-07
期刊：
影响因子：
--
通讯作者：
Marshak-Rothstein A
中科院分区：
文献类型：
--
作者：
Lau CM;Broughton C;Tabor AS;Akira S;Flavell RA;Mamula MJ;Christensen SR;Shlomchik MJ;Viglianti GA;Rifkin IR;Marshak-Rothstein A
先前的研究（Leadbetter，E.A.，I.R. Rifkin，A.H.霍尔鲍姆B Beaudette、M.J. Shlomchik和A.马歇尔-罗斯坦公司2002.自然416：603-607; Viglianti，G.A.，C.M. Lau，T.M.汉利，文学士Miko，M.J. Shlomchik，and A.马歇尔-罗斯坦公司2003.免疫力19：837-847）建立了DNA和DNA相关自身抗原通过B细胞抗原受体（BCR）和Toll样受体（TLR）的顺序接合来激活自身反应性B细胞的独特能力9。我们证明，这两个受体的范例可以扩展到BCR/TLR 7激活的自身反应性B细胞的RNA和RNA相关的自身抗原。这些数据暗示TLR识别内源性配体的DNA和RNA相关的自身抗原的反应。重要的是，IFN-α显著增强了对RNA相关自身抗原的反应，IFN-α是一种与系统性红斑狼疮（SLE）患者疾病进展密切相关的细胞因子。作为TLR在SLE自身抗体应答中发挥关键作用的进一步证据，我们发现缺乏TLR衔接蛋白MyD 88的自身免疫易感小鼠的染色质、Sm和类风湿因子自身抗体滴度显著降低。
Previous studies (Leadbetter, E.A., I.R. Rifkin, A.H. Hohlbaum, B. Beaudette, M.J. Shlomchik, and A. Marshak-Rothstein. 2002. Nature. 416:603–607; Viglianti, G.A., C.M. Lau, T.M. Hanley, B.A. Miko, M.J. Shlomchik, and A. Marshak-Rothstein. 2003. Immunity. 19:837–847) established the unique capacity of DNA and DNA-associated autoantigens to activate autoreactive B cells via sequential engagement of the B cell antigen receptor (BCR) and Toll-like receptor (TLR) 9. We demonstrate that this two-receptor paradigm can be extended to the BCR/TLR7 activation of autoreactive B cells by RNA and RNA-associated autoantigens. These data implicate TLR recognition of endogenous ligands in the response to both DNA- and RNA-associated autoantigens. Importantly, the response to RNA-associated autoantigens was markedly enhanced by IFN-α, a cytokine strongly linked to disease progression in patients with systemic lupus erythematosus (SLE). As further evidence that TLRs play a key role in autoantibody responses in SLE, we found that autoimmune-prone mice, lacking the TLR adaptor protein MyD88, had markedly reduced chromatin, Sm, and rheumatoid factor autoantibody titers.
登录
查看更多内容
DOI：
10.1111/j.1749-6632.2003.tb06053.x
发表时间：
2003-01-01
期刊：
IMMUNE MECHANISMS AND DISEASE
影响因子：
--
作者：
Pollard, KM;Hultman, P;Kono, DH
通讯作者：
Kono, DH
Toll样受体9控制鼠狼疮中的抗DNA自身抗体产生。
DOI：
10.1084/jem.20050338
发表时间：
2005-07-18
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Christensen SR;Kashgarian M;Alexopoulou L;Flavell RA;Akira S;Shlomchik MJ
通讯作者：
Shlomchik MJ
影响因子：
32.4
作者：
Jego, G;Palucka, AK;Banchereau, J
通讯作者：
Banchereau, J
影响因子：
11.4
作者：
Häcker, H;Mischak, H;Wagner, H
通讯作者：
Wagner, H
影响因子：
32.4
作者：
Viglianti, GA;Lau, CM;Rothstein, AM
通讯作者：
Rothstein, AM