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阿里碳化合物受体调节IL-22受体表达在胸膜上皮细胞上,并加速胸膜再生
Jingyi Shen1,2, Ying Wang1,2, Fei Zheng1,2
1Blood Diseases Institute, Xuzhou Medical University, Xuzhou, 221002, China.
NPJ Regenerative medicine
|November 8, 2023
概括
基碳化合物受体 (AHR) 通过调节基上皮细胞中的IL-22受体1 (IL-22RA1) 表达来增强胸腺再生. 这一发现为改善T细胞免疫力和管理移植与宿主疾病提供了新的策略.
科学领域:
- 免疫学 免疫学 免疫学
- 发展生物学 发展生物学
- 分子生物学分子生物学
背景情况:
- 甲状腺再生对于在损伤后恢复T细胞免疫力至关重要.
- 干白素-22 (IL-22) 通过帮助胸膜上皮细胞 (TECs) 来促进胸膜再生.
- IL-22受体IL-22RA1调解IL-22功能,但其调节机制尚不清楚.
研究的目的:
- 为了研究瘤再生中的基碳化合物受体 (AHR) 的作用.
- 阐明AHR影响IL-22RA1表达的机制.
- 评估针对甲状腺再生和慢性移植与宿主疾病 (cGVHD) 的AHR和IL-22RA1治疗潜力.
主要方法:
- 使用了TECs条件淘汰的小鼠 (Foxn1-cre介导的AHR淘汰).
- 使用的AHR抑制剂 (CH-223191) 和激动剂 (FICZ).
- 在mTEC1细胞中使用染色体免疫沉降和光酶记者测定.
- 产生的IL-22RA1淘汰赛小鼠 (Foxn1-cre介导的IL-22RA1淘汰赛).
主要成果:
- AHR淘汰赛显著损害了胸腺再生,外源IL-222无法挽救.
- AHR直接与IL-22RA1基因促进体结合,通过转录上调其表达.
- 向AHR或IL-22RA1调节了小鼠cGVHD的严重程度,与胸腺再生和T细胞复合相关.
结论:
- 由TECs表达的AHR在甲状腺再生中起着至关重要的,以前未被认可的作用.
- AHR通过转录来调节IL-22RA1的表达,将AHR信号与IL-22-介导的胸腺恢复联系起来.
- 调节AHR和IL-22RA1为改善胸腺再生和管理cGVHD提供了潜在的治疗策略.
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