在口服诱导的调节性T细胞群体中,不同的功能和转录特征
Moanaro Biswas1, Kaman So2, Thais B Bertolini1
1Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, United States.
Frontiers in immunology
|November 13, 2023
概括
口服抗原诱导多个调节性T细胞 (Treg) 子集,抑制抗体的产生. 这些独特的Treg细胞,FoxP3+LAP+和FoxP3-LAP+,共同控制免疫反应.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
背景情况:
- 口服抗原可以诱导免疫耐受性.
- 调节性T细胞 (Treg) 在维持免疫平衡中起着至关重要的作用.
- 了解Treg子集是开发免疫调节策略的关键.
研究的目的:
- 调查通过口服抗原给药诱导的CD4+Treg亚组的独特作用和特征.
- 阐明这些Treg子集调解系统性抑制的机制.
- 探索这些Treg子集在像血友病这样的疾病中管理免疫反应的潜力.
主要方法:
- 血友病的小鼠模型.
- 流细胞计和单细胞转录组分析.
- 功能性测试以评估T细胞抑制和细胞因子生产.
主要成果:
- 口服抗原诱导了三个CD4+Treg子组:FoxP3+LAP-,FoxP3+LAP+和FoxP3-LAP+.这些子组分别为FoxP3+LAP+,FoxP3+LAP+和FoxP3-LAP+.
- FoxP3+LAP+细胞代表了FoxP3+LAP-Treg的激活形式,其特征是增加IL-2Rα和TCR信号传递.
- 虽然FoxP3-LAP+细胞表达的TCR信号较少,但它们对IL-10产生具有显著的AP-1复合体参与 (Jun/Fos,Atf3).
- 福克斯P3+LAP+和福克斯P3-LAP+细胞都能有效地抑制传统的T细胞,并可以诱导FoxP3的表达,而FoxP3-LAP+细胞可能会转化为FoxP3+Treg.
- TGF-β的表达依赖于Jun/Fos转录因子,通过FoxP3+LAP+或FoxP3-LAP+细胞的IL-2Rα依赖或独立通路进行介导.
结论:
- 口服诱导的免疫抑制涉及多种具有互补功能的调节性T细胞类型.
- 独特的Treg子集,FoxP3+LAP+和FoxP3-LAP+,合作抑制全身抗体的产生.
- 这些发现提供了对口服耐受性和免疫介导疾病潜在治疗点的复杂机制的见解.
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