TACI和BCMA是TNF同类体的受体,与B细胞自身免疫性疾病有关
J A Gross1, J Johnston, S Mudri
1Department of Immunology, ZymoGenetics, Seattle, Washington 98102, USA. grossj@zgi.com
Nature
|May 9, 2000
概括
B细胞因子zTNF4 (B细胞激活因子) 和它的受体与狼等自身免疫性疾病有关. 通过TACI-Ig阻止zTNF4显示出治疗这些疾病的前景.
科学领域:
- 免疫学 免疫学 免疫学
- 自免疫性疾病 自免疫性疾病
- 分子生物学分子生物学
背景情况:
- 在自身免疫性疾病中,B细胞通过激活,自身抗体产生和T细胞共同刺激发挥关键作用.
- 瘤亡因子连接体家族成员zTNF4 (B细胞激活因子) 是一种强大的B细胞联合激活剂.
研究的目的:
- 确定zTNF4的受体,并研究其在自身免疫性疾病中的作用.
- 评估TACI-Ig作为自身免疫性疾病的潜在治疗方法.
主要方法:
- 转基因动物中zTNF4的过度表达.
- 在易患自身免疫性小鼠模型中定量循环中的zTNF4.
- 对zTNF4受体的鉴定 (TACI和BCMA).
- 用可溶性TACI-Ig融合蛋白对小鼠进行治疗.
主要成果:
- 过度表达zTNF4的转基因动物表现出类似狼的症状,并扩大了特定的B细胞群.
- 在小鼠模型中,在狼发作和进展期间观察到循环中zTNF4水平升高.
- TACI和BCMA被确定为zTNF4受体.
- 在NZBWF1小鼠中,TACI-Ig治疗减少了蛋白尿和改善了生存率.
结论:
- zTNF4及其受体与系统性红斑狼 (SLE) 的病原发生有关.
- TACI-Ig证明了治疗自身免疫性疾病的治疗潜力,包括人类SLE.
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