BLyS and APRIL form biologically active heterotrimers that are expressed in patients with systemic immune-based rheumatic diseases
BLyS and APRIL form biologically active heterotrimers that are expressed in patients with systemic immune-based rheumatic diseases
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DOI：
10.4049/jimmunol.169.8.4314
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发表时间：
2002-10-15
影响因子：
4.4
通讯作者：
Migone, TS
中科院分区：
文献类型：
--
作者：
Roschke, V;Sosnovtseva, S;Migone, TS
BLyS和APRIL是TNF超家族的两个成员，由活化的髓样细胞分泌，对B细胞具有共刺激活性。BLyS和APRIL共有两种受体TACI和BCMA，而第三种受体BAFF-R特异性结合BLyS。BLyS和APRIL都被描述为同源三聚体分子，这是TNF超家族成员共有的特征。在这项研究中，我们表明，APRIL和BLyS可以形成积极的异源三聚体分子时，共表达和循环异源三聚体存在于血清样本中的系统性免疫为基础的风湿性疾病患者。这些发现提高了活性BLyS/APRIL异源三聚体可能在风湿性和其他自身免疫性疾病中发挥作用的可能性，并且TNF配体超家族的其他成员也可能形成活性可溶性异源三聚体。
BLyS and APRIL are two members of the TNF superfamily that are secreted by activated myeloid cells and have costimulatory activity on B cells. BLyS and APRIL share two receptors, TACI and BCMA, whereas a third receptor, BAFF-R, specifically binds BLyS. Both BLyS and APRIL have been described as homotrimeric molecules, a feature common to members of the TNF superfamily. In this study, we show that APRIL and BLyS can form active heterotrimeric molecules when coexpressed and that circulating heterotrimers are present in serum samples from patients with systemic immune-based rheumatic diseases. These findings raise the possibility that active BLyS/APRIL heterotrimers may play a role in rheumatic and other autoimmune diseases and that other members of the TNF ligand superfamily may also form active soluble heterotrimers.