BLyS and APRIL in rheumatoid arthritis
BLyS and APRIL in rheumatoid arthritis
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DOI：
10.1172/jci25265
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发表时间：
2005-11-01
影响因子：
15.9
通讯作者：
Weyand, CM
中科院分区：
文献类型：
--
作者：
Seyler, TM;Park, YW;Weyand, CM
细胞因子 B 淋巴细胞刺激剂 (BLyS) 和增殖诱导配体 (APRIL) 通过维持 B 细胞活化来增强自身免疫性疾病。在 RA 中，B 细胞有助于在发炎滑膜中形成 3 种功能不同类型的淋巴微结构：异位 GC； T细胞-B细胞聚集体缺乏GC反应；以及无组织的、弥漫性的渗透。我们检查了代表 3 种滑膜炎的 72 个组织的 BLyS 和 APRIL 产生以及 APRIL/BLyS 受体的表达。通过用 APRIL 和 BLyS 诱饵受体跨膜激活剂和 CAML 相互作用子:Fc (TACI:Fc) 处理人滑膜-SCID 小鼠嵌合体，探索 BLyS 和 APRIL 的生物学效应。 GC(+)滑膜炎的APRIL水平最高，仅由CD83(+) DC产生。 BLyS 在所有组织类型中都以相似的水平存在，并且仅源自 CD68(+) 巨噬细胞。在 GC(+) 滑膜炎中，TACI:Fc 治疗导致 GC 破坏并显着抑制 IFN-γ 和 Ig 转录。相反，在聚集性和弥漫性滑膜炎中抑制 APRIL 和 BLyS 不会影响 Ig 水平，并增强 IFN-γ 的产生。这些不同的免疫调节作用与聚集性和弥漫性滑膜炎中存在 TACI(+) T 细胞以及 GC(+) 滑膜炎中不存在 TACI(+) T 细胞相关。我们认为 BLyS 和 APRIL 调节 B 细胞和 T 细胞功能，并在 RA 中具有促炎和抗炎活性。
The cytokines B lymphocyte stimulator (BLyS) and a proliferation-inducing ligand (APRIL) enhance autoimmune disease by sustaining B cell activation. In RA, B cells contribute to the formation of 3 functionally distinct types of lymphoid microarchitectures in the inflamed synovium: ectopic GCs; T cell-B cell aggregates lacking GC reactions; and unorganized, diffuse infiltrates. We examined 72 tissues representing the 3 types of synovitis for BLyS and APRIL production and for expression of APRIL/BLyS receptors. Biologic effects of BLyS and APRIL were explored by treating human synovium-SCID mouse chimeras with the APRIL and BLyS decoy receptor transmembrane activator and CAML interactor:Fc (TACI:Fc). GC(+) synovitis had the highest levels of APRIL, produced exclusively by CD83(+) DCs. BLyS was present in similar levels in all tissue types and derived exclusively from CD68(+) macrophages. In GC(+) synovitis, treatment with TACI:Fc resulted in GC destruction and marked inhibition of IFN-gamma and Ig transcription. In contrast, inhibition of APRIL and BLyS in aggregate and diffuse synovitis left Ig levels unaffected and enhanced IFN-gamma production. These differential immunomodulatory effects correlated with the presence of TACI(+) T cells in aggregate and diffuse synovitis and their absence in GC(+) synovitis. We propose that BLyS and APRIL regulate B cell as well as T cell function and have pro- and antiinflammatory activities in RA.