Function of the Bone Morphogenetic Protein in Immune System

骨形态发生蛋白在免疫系统中的功能

• 批准号: 15580269
• 负责人: OGAWA Kenji
• 金额: $ 2.05万
• 依托单位: RIKEN
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15580269/
• 关键词: TGF-β; T-cell; TGF-beta; BMP; リンパ球; マクロファージ

Activins, members of the transforming growth factor-b(TGF-β) superfamily, are pluripotent growth and differentiation factors. In many biological systems, activins have overlapping biological activities with TGF-β partly due to the fact that activins and TGF-bs utilize the same proteins (Smad2 and/or Smad3) in signal transduction. The expression and function of activin in the immune system are not yet fully characterized, in contrast to the extensive knowledge of TGF-β's functions. It inhibits the proliferation and differentiation into effector cells, and induces the apoptosis in T cells. We investigated the regulatory expression of activin A in CD4^+ helper T cells. Our results revealed that activin A is produced by CD4^+T cells in response to their activation. In recent years, CD4+CD25+ regulatory T cells have emerged as a unique population of suppressor T cells that produce high levels of TGF-β that is involved in maintaining peripheral immune tolerance. We determined if activin A is produced in CD4^+CD25^+T cells and acts as a suppressor of T cell functions. Activin expression was not detected in CD4^+CD25^+ regulatory T cells even when they were stimulated with anti-CD3 and anti-CD28 mAbs, although TGF-b1 was highly expressed. Addition of activin A, follistatin or anti-activin mAb to the culture barely affected the in vitro suppression of T cell proliferation by CD4^+CD25^+ regulatory T cells. In contrast, TGF-β1 but not activin A efficientiy inhibited T-cell proliferation in a dose-dependent manner. Thus, the function ofactivin is distinct from that of TGF-β at least on the proliferation of CD4^+ T cells.

激活素是转化生长因子-b (TGF-β) 超家族的成员，是多能生长和分化因子。在许多生物系统中，激活素与 TGF-β 具有重叠的生物活性，部分原因是激活素和 TGF-b 在信号转导中利用相同的蛋白质（Smad2 和/或 Smad3）。与对 TGF-β 功能的广泛了解相比，激活素在免疫系统中的表达和功能尚未完全表征。它抑制增殖和分化为效应细胞，并诱导T细胞凋亡。我们研究了 CD4^+ 辅助 T 细胞中激活素 A 的调节表达。我们的结果表明，激活素 A 是由 CD4^+T 细胞响应其激活而产生的。近年来，CD4+CD25+调节性T细胞作为一种独特的抑制性T细胞群体出现，可产生高水平的TGF-β，参与维持外周免疫耐受。我们确定了激活素 A 是否在 CD4^+CD25^+T 细胞中产生并充当 T 细胞功能的抑制剂。尽管 TGF-b1 高度表达，但即使用抗 CD3 和抗 CD28 mAb 刺激，CD4^+CD25^+ 调节性 T 细胞中也未检测到激活素表达。向培养物中添加激活素 A、卵泡抑素或抗激活素单克隆抗体几乎不影响 CD4^+CD25^+ 调节性 T 细胞对 T 细胞增殖的体外抑制。相反，TGF-β1（而非激活素 A）以剂量依赖性方式有效抑制 T 细胞增殖。因此，激活素的功能至少在CD4+T细胞的增殖方面不同于TGF-β。