Lack of T cells in Act1-deficient mice results in elevated IgM-specific autoantibodies but reduced lupus-like disease.
Lack of T cells in Act1-deficient mice results in elevated IgM-specific autoantibodies but reduced lupus-like disease.
复制标题
DOI：
10.1002/eji.201142238
复制
发表时间：
2012-07
影响因子：
5.4
通讯作者：
Jorgensen, Trine N.
中科院分区：
文献类型：
--
作者：
Johnson, Angela C.;Davison, Laura M.;Giltiay, Natalia V.;Vareechon, Chairut;Li, Xiaoxia;Jorgensen, Trine N.
Act1是BAFF和cd40l诱导的信号传导的负调节因子。缺乏Act1的Balb/c小鼠会产生类似系统性红斑狼疮（SLE）和Sjögren综合征（SjS）的系统性自身免疫。SLE和SjS的特点是产生抗核IgG自身抗体（ANA-IgG）和周围组织炎症。由于自身抗体的产生可以以t细胞依赖或t细胞独立的方式发生，我们研究了t细胞在act1介导的自身免疫中的作用。在C57Bl/6 （B6. act1−/−）小鼠和B6上培养act1缺乏症小鼠。生成TCRβ−/−TCRδ−/−Act1−/−(TKO)小鼠。而TCRβ/δ-充足的B6。Act1−/−小鼠出现脾肿大和淋巴结病变、高γ球蛋白血症、ANA-IgG水平升高和肾脏病理，TKO小鼠未出现任何此类疾病迹象。无论是B6。Act1−/−或TKO小鼠出现sjs样疾病，表明Balb/c背景上的表观遗传相互作用是导致Balb/c表型的原因。Act1−−老鼠。有趣的是，先前在Balb/c中报道的baff驱动的移行性B细胞异常。Act1−/−小鼠，在B6中完好无损。Act1−/−小鼠，很大程度上独立于T细胞。综上所述，T细胞在B6的slea样疾病的发展中是必需的。Act1−/−小鼠，而不是baff驱动的过渡性b细胞分化。
Act1 is a negative regulator of BAFF and CD40L-induced signaling. Balb/c mice lacking Act1 develop systemic autoimmunity resembling Systemic Lupus Erythematosus (SLE) and Sjögren's Syndrome (SjS). SLE and SjS are characterized by anti-nuclear IgG autoantibody (ANA-IgG) production and inflammation of peripheral tissues. As autoantibody production can occur in a T-cell dependent or T-cell independent manner, we investigated the role of T-cell help during Act1-mediated autoimmunity. Act1-deficiency was bred onto C57Bl/6 (B6.Act1−/−) mice and B6.TCRβ−/−TCRδ−/−Act1−/− (TKO) mice were generated. While TCRβ/δ-sufficient B6.Act1−/− mice developed splenomegaly and lymphadenopathy, hypergammaglobulinemia, elevated levels of ANA-IgG, and kidney pathology, TKO mice failed to develop any such signs of disease. Neither B6.Act1−/− nor TKO mice developed SjS-like disease, suggesting that epigenetic interactions on the Balb/c background are responsible for this phenotype in Balb/c.Act1−/− mice. Interestingly, BAFF-driven transitional B cell abnormalities, previously reported in Balb/c.Act1−/− mice, were intact in B6.Act1−/− mice and largely independent of T cells. In conclusion, T cells are necessary for the development of SLE-like disease in B6.Act1−/− mice, but not BAFF-driven transitional B-cell differentiation.
登录
查看更多内容
脾脏中的B细胞发育发生在离散的步骤中，并取决于B细胞受体衍生的信号的质量。
影响因子：
15.3
作者：
Loder, F;Mutschler, B;Ray, R J;Paige, C J;Sideras, P;Torres, R;Lamers, M C;Carsetti, R
通讯作者：
Carsetti, R
影响因子：
3.7
作者：
Chang, Nan-Hua;Cheung, Yui-Ho;Wither, Joan
通讯作者：
Wither, Joan
影响因子：
30.5
作者：
Doreau, Agnes;Belot, Alexandre;Bonnefoy-Berard, Nathalie
通讯作者：
Bonnefoy-Berard, Nathalie
影响因子：
4.4
作者：
Higuchi, T;Aiba, Y;Tsubata, T
通讯作者：
Tsubata, T
影响因子：
4.4
作者：
Batten, M;Fletcher, C;Mackay, F
通讯作者：
Mackay, F