调控性B细胞通过依赖IL-21的同源相互作用控制T细胞自身免疫力
Ayumi Yoshizaki1, Tomomitsu Miyagaki, David J DiLillo
1Department of Immunology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Nature
|October 16, 2012
概括
调节性B细胞 (B10细胞) 产生互白素-10 (IL-10) 可以抑制自身免疫性疾病. T细胞相互作用和IL-21对B10细胞功能至关重要,提供潜在的新疗法.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 这是一种自身免疫力.
背景情况:
- B细胞是免疫反应的关键调节者,主要通过抗体的产生.
- 某些被称为调控性B细胞 (B10细胞) 的B细胞子集,可以通过分泌互白素-10 (IL-10) 来抑制免疫反应.
- B10细胞是小鼠T细胞依赖的自身免疫疾病的强有力的调节者,但它们在体内调节的作用尚未完全理解.
研究的目的:
- 在体内研究控制B10细胞IL-10产生和免疫调节的机制.
- 探索ex vivo扩展B10细胞作为自身免疫性疾病治疗策略的潜力.
主要方法:
- 利用多发性硬化症的小鼠模型研究B10细胞功能.
- 研究了IL-21和CD40依赖的T细胞相互作用在B10细胞成熟中的作用.
- 使用CD40和IL-21受体信号进行了B10细胞的活体扩张.
- 将扩展的B10细胞转移到已确定的自身免疫性疾病的小鼠中.
主要成果:
- B10细胞成长为IL-10分泌效应细胞需要IL-21和CD40依赖的T细胞亲属相互作用.
- 使用CD40和IL-21受体信号的B10细胞的活体扩张导致了400万倍的增加.
- 采用扩大B10细胞的转移显著抑制了小鼠自身免疫性疾病的症状.
结论:
- 在体内,IL-21和T细胞的相互作用对IL-10产生的B10细胞的发育和功能至关重要.
- 自体B10细胞的ex vivo扩张和再注入代表了严重自身免疫性疾病的有前途的治疗方法.
- 这一策略可能为抵抗当前治疗方法的自身免疫疾病提供一种新的治疗方法.
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