CD11c-mediated deletion of Flip promotes autoreactivity and inflammatory arthritis.
CD11c-mediated deletion of Flip promotes autoreactivity and inflammatory arthritis.
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CD11C介导的翻转缺失可促进自动反应性和炎症性关节炎。
DOI：
10.1038/ncomms8086
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发表时间：
2015-05-12
影响因子：
16.6
通讯作者：
Pope, Richard M.
中科院分区：
文献类型：
--
作者：
Huang, Qi-Quan;Perlman, Harris;Birkett, Robert;Doyle, Renee;Fang, Deyu;Haines, G. Kenneth;Robinson, William;Datta, Syamal;Huang, Zan;Li, Quan-Zhen;Phee, Hyewon;Pope, Richard M.
树突状细胞（dc）对免疫稳态至关重要。为了靶向dc，我们在CD11c启动子（CD11c-Flip- ko）下表达cre的细胞中产生了一个Flip缺陷的小鼠系。CD11c-Flip-KO小鼠自发地发展为侵蚀性炎性关节炎，类似于类风湿关节炎，当这些小鼠与Rag - / -小鼠杂交时，这种情况显著减少。CD8α+ DC亚群显著减少，同时NK细胞和巨噬细胞也发生改变。关节组织中存在自身反应性CD4+ T细胞和自身抗体，关节炎的严重程度与关节引流淋巴结中自身反应性CD4+ T细胞和质母细胞的数量相关。减少的T调节细胞（Tregs）与关节炎的严重程度呈负相关，Tregs的转移可以改善关节炎。这个KO系确定了一个模型，将允许深入探究类风湿关节炎的发病机制，包括CD8α+ dc和其他免疫系统细胞的作用。树突状细胞对启动免疫反应和诱导耐受至关重要。在这里，作者表明，cd11c表达细胞亚群中生存因子c-flip的缺失会扰乱CD8a+树突状细胞、NK和巨噬细胞池，并导致自身免疫性关节炎的发展。
Dendritic cells (DCs) are critical for immune homeostasis. To target DCs, we generated a mouse line with Flip deficiency in cells that express cre under the CD11c promoter (CD11c-Flip-KO). CD11c-Flip-KO mice spontaneously develop erosive, inflammatory arthritis, resembling rheumatoid arthritis, which is dramatically reduced when these mice are crossed with Rag−/− mice. The CD8α+ DC subset is significantly reduced, along with alterations in NK cells and macrophages. Autoreactive CD4+ T cells and autoantibodies specific for joint tissue are present, and arthritis severity correlates with the number of autoreactive CD4+ T cells and plasmablasts in the joint-draining lymph nodes. Reduced T regulatory cells (Tregs) inversely correlate with arthritis severity, and the transfer of Tregs ameliorates arthritis. This KO line identifies a model that will permit in depth interrogation of the pathogenesis of rheumatoid arthritis, including the role of CD8α+ DCs and other cells of the immune system. Dendritic cells are critical for initiation of immune responses and for induction of tolerance. Here the authors show that deletion of survival factor c-flip in CD11c-expressing cells subset perturbs CD8a+ dendritic cell, NK and macrophage pools, and leads to development of autoimmune arthritis.
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DOI：
10.1038/nri3477
发表时间：
2013-08
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
13.3
作者：
Huang, Qi-Quan;Birkett, Robert;Pope, Richard M.
通讯作者：
Pope, Richard M.
影响因子：
20.3
作者：
Huang, Qi-Quan;Perlman, Harris;Pope, Richard M.
通讯作者：
Pope, Richard M.
影响因子：
9.1
作者：
Gueguen, Paul;Dalekos, Georgios;Renaudineau, Yves
通讯作者：
Renaudineau, Yves
DOI：
10.1084/jem.20041457
发表时间：
2004-10-18
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Gallegos AM;Bevan MJ
通讯作者：
Bevan MJ