TFEB调节树突细胞抗原的呈现,以调节喘中的免疫平衡
JinYing Xiang1, Bo Liu2, Yan Li1
1Department of Respiratory Medicine, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Engineering Research Center of Stem Cell Therapy, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation base of Child development and Critical Disorders, Children's Hospital of Chongqing Medical University, No. 136, Zhongshan 2nd Road, Yuzhong Dis, 400014, Chongqing, PR China.
转录因子EB (TFEB) 在儿科喘中升高,导致树突细胞功能障碍和T细胞失衡. 沉默TFEB可以恢复免疫恒温,这表明TFEB是喘的治疗点.
科学领域:
- 免疫学和呼吸系统医学
- 分子生物学和遗传学分子生物学和遗传学
背景情况:
- 儿童喘的发病包括树突细胞 (DC) 抗原呈现和T细胞子集不平衡.
- 转录因子EB (TFEB) 在这个过程中的作用尚未完全理解.
研究的目的:
- 研究TFEB在DC抗原呈现和T细胞分化在儿科喘中的作用.
- 探索TFEB作为喘潜在的治疗点.
主要方法:
- 室内灰尘 (HDM) 激活的骨髓衍生的树突细胞 (BMDCs) 的RNA测序.
- 在患有喘和没有喘的儿童的外周血液单核细胞 (PBMC) 中进行TFEB mRNA表达分析.
- 在HDM诱导的喘小鼠模型中对TFEB的体内评估以及在T细胞的体外共同培养实验.
主要成果:
- TFEB被确定为与免疫路径和抗原呈现相关的差异表达基因.
- 在喘儿童的PBMC和喘小鼠的肺DC中,TFEB表达显著增加.
- 在DCs下调的抗原呈现分子 (MHC II,CD80,CD86,CD40),重新平衡的T细胞子集 (Th1/Th2,Th17/Treg) 和调节的细胞因子配置 (减少IL-4,IL-5,IL-13,IL-17;增加IL-10) 中进行TFEB沉默.
结论:
- 通过影响DC抗原呈现,T细胞分化和细胞因子分泌,TFEB在喘发育中起着至关重要的作用.
- 调节TFEB可能会恢复喘中的免疫平衡.
- 这些发现表明,TFEB是喘治疗的潜在新型治疗标.
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