细胞内膜网膜应激反应调解器 IRE-1α 促进移植对宿主疾病发展中的宿主树突细胞
Hee-Jin Choi1,2,3, Yongxia Wu1,2,3, Brianyell McDaniel Mims4
1Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, WI.
Journal of immunology (Baltimore, Md. : 1950)
|June 12, 2024
概括
在树突细胞 (DCs) 中准内质网膜应激调解器IRE-1α可以在移植后抑制移植对宿主疾病 (GVHD). 这种方法保留了移植与白血病的反应,为改善移植结果提供了一个有希望的策略.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 在瘤学瘤学.
背景情况:
- 全基性造血细胞移植是血液恶性瘤的重要治疗方法.
- 移植与宿主疾病 (GVHD) 和调节方案可以诱导内分泌网膜 (ER) 应激.
- IRE-1α信号通路,包括拼接的XBP-1 (XBP-1s) 和RIDD,在免疫反应中起作用.
研究的目的:
- 研究IRE-1α-XBP-1s信号传导在树突细胞 (DC) 功能和GVHD中的作用.
- 评估用于治疗GVHD的宿主DC中抑制IRE-1α的治疗潜力.
- 确定XBP-1s和RIDD在DC全活性和GVHD病变发生中的贡献.
主要方法:
- 使用了特定于直流的XBP-1缺乏的小鼠 (捐赠者或接受者).
- 在移植前向接受者小鼠注射了一种IRE-1α抑制剂 (B-I09).
- 在体内和体外评估了DC存活率,全活性,T细胞增殖和GVHD发育.
主要成果:
- 宿主DC中的XBP-1s对于GVHD诱导至关重要,但对于移植与白血病反应却不至关重要.
- 接受者的IRE-1α抑制显著抑制了GVHD,同时保持了抗白血病效应.
- 抑制IRE-1α降低了DC存活率和全活性,损害了T细胞的激活和增殖.
- 发现XBP-1s和RIDD都对最佳DC激活和GVHD至关重要.
结论:
- 主体DC XBP-1s和由IRE-1α信号介导的RIDD通路对于GVHD病变发生至关重要.
- 在宿主DC中准IRE-1α代表了一种潜在的治疗策略,以减轻移植后的GVHD.
- 这种方法提供了一种方法,可以将移植与白血病效应与GVHD分开,从而提高移植疗效.
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