C1q deficiency leads to the defective suppression of IFN-alpha in response to nucleoprotein containing immune complexes.
C1q deficiency leads to the defective suppression of IFN-alpha in response to nucleoprotein containing immune complexes.
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DOI：
10.4049/jimmunol.1001731
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发表时间：
2010-10-15
期刊：
影响因子：
--
通讯作者：
Elkon KB
中科院分区：
文献类型：
--
作者：
Santer DM;Hall BE;George TC;Tangsombatvisit S;Liu CL;Arkwright PD;Elkon KB
几乎所有患有C1q纯合子缺乏症的人都会患上系统性红斑狼疮（SLE）。C1q阻止SLE发展的确切细胞机制尚不清楚。在本研究中，我们在体外测试了C1q在免疫复合物（ICs）诱导的IFN-α调节中的作用，以及体内缺乏C1q的后果。我们的实验显示，C1q优先促进SLE ic与单核细胞的结合，而不是浆细胞样树突状细胞，但这种抑制不是由于抑制性可溶性因子的诱导。C1q的存在也改变了单核细胞内ic的运输，使得ic在早期核内体中持续存在。在C1q缺乏症患者中，血清和脑脊液中IFN-α和IFN-γ -诱导蛋白-10水平升高，并与Ro自身抗体密切相关，证明了这些观察结果的临床意义。因此，这些研究将C1q缺陷与IFN-α调节缺陷联系起来，并提供了C1q阻止ic刺激自身免疫发展的细胞机制的更好理解。
Almost all humans with homozygous deficiency of C1q develop systemic lupus erythematosus (SLE). The precise cellular mechanism (s) by which C1q prevents the development of SLE remains unclear. In this study, we tested the role of C1q in the regulation of IFN-α induced by immune complexes (ICs) in vitro, as well as the consequences of lack of C1q in vivo. Our experiments revealed that C1q preferentially promotes the binding of SLE ICs to monocytes rather than plasmacytoid dendritic cells, but this inhibition was not due to the induction of inhibitory soluble factors. The presence of C1q also altered the trafficking of ICs within monocytes such that ICs persisted in early endosomes. In patients with C1q deficiency, serum and cerebrospinal fluid levels of IFN-α and IFN-γ–inducible protein-10 levels were elevated and strongly correlated with Ro autoantibodies, demonstrating the clinical significance of these observations. These studies therefore associate C1q deficiency with defective regulation of IFN-α and provide a better understanding of the cellular mechanisms by which C1q prevents the development of IC-stimulated autoimmunity.
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影响因子：
4.6
作者：
Kong, K. O.;Tan, A. W.;Howe, H. S.
通讯作者：
Howe, H. S.
DOI：
10.1084/jem.20021553
发表时间：
2003-03-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Bennett L;Palucka AK;Arce E;Cantrell V;Borvak J;Banchereau J;Pascual V
通讯作者：
Pascual V
影响因子：
--
作者：
Eloranta, Maija-Leena;Lovgren, Tanja;Ronnblom, Lars
通讯作者：
Ronnblom, Lars
DOI：
10.1084/jem.185.6.1101
发表时间：
1997-03-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Grouard G;Rissoan MC;Filgueira L;Durand I;Banchereau J;Liu YJ
通讯作者：
Liu YJ
影响因子：
2.6
作者：
Bengtsson, AA;Sturfelt, G;Rönnblom, L
通讯作者：
Rönnblom, L