细胞外膀介导的复合IL-10通过减少胎儿炎症反应来防止与感染相关的早产
Ananth Kumar Kammala1, Angela Mosebarger1, Enkhtuya Radnaa1
1Division of Basic Science and Translational Research, Department of Obstetrics & Gynecology, The University of Texas Medical Branch at Galveston, Galveston, TX, United States.
Frontiers in immunology
|August 21, 2023
概括
携带互白素-10 (IL-10) 的工程外细胞囊泡 (EVs) 在小鼠中安全延迟感染诱导的早产. 这种新的治疗方法减少了胎儿的炎症,并导致生育期的活产.
科学领域:
- 产科和妇科 产科和妇科
- 免疫学 免疫学 免疫学
- 生物技术是生物技术.
背景情况:
- 由免疫细胞透和子宫组织中NF-κB激活驱动的胎儿炎症反应是感染相关的早产 (PTB) 的主要原因.
- 尽量减少炎症对于减少PTB发病率至关重要.
研究的目的:
- 为了设计载有抗炎性细胞因子10 (IL-10) 的细胞外囊泡 (EV),用于治疗感染诱导的PTB.
- 为了评估这些工程 EVs (eIL-10) 的有效性,在细菌性阴道炎诱导的PTB的小鼠模型中.
主要方法:
- 来自HEK293T细胞的EV被用IL-10进行电穿孔,以产生eIL-10.
- 在试验室中评估了eIL-10的结构和功能特征.
- 鼠被感染大肠杆菌诱导PTB,并用PBS,eIL-10,Gentamicin或组合治疗.
- 在转基因小鼠模型中,使用CyTOF分析了胎儿的炎症反应.
主要成果:
- 工程 EVs (eIL-10) 在结构和功能上稳定,在体外减少了促炎性细胞因子的产生.
- 给母亲服用eIL-10穿越了胎儿与母亲之间的障碍,延迟了大肠杆菌诱导的PTB,并导致了早产活产.
- 使用eIL-10的治疗显著降低了子宫炎症,包括免疫细胞透,组织学肌炎,NF-κB激活和促炎细胞因子水平.
结论:
- eIL-10的使用是安全,稳定和特异性的,有效地将PTB延迟超过72小时,并使活产婴儿.
- 使用EV用于药物输送克服了与子宫内胎儿干预相关的局限性.
- 在EV中封装IL-10,消除了直接胚胎给药的需要,提高了治疗疗效和安全性.
相关概念视频
01:22Development of Immunocompetence
342
The initiation of cell-mediated immunity can be observed as early as the third month of fetal growth, with active antibody-mediated immunity following approximately one month later.
The initial cells that migrate from the fetal thymus settle within the skin and epithelial tissues lining the mouth, digestive tract, and in females, the uterus and vagina. These cells, including skin-based dendritic cells, serve as antigen-presenting cells, playing a key role in T cell activation.
Subsequent T...
The initial cells that migrate from the fetal thymus settle within the skin and epithelial tissues lining the mouth, digestive tract, and in females, the uterus and vagina. These cells, including skin-based dendritic cells, serve as antigen-presenting cells, playing a key role in T cell activation.
Subsequent T...
342
01:15Transcytosis of IgG
2.8K
Transcytosis is the process in which molecules are internalized by endocytosis, transported across the cell, and released through exocytosis from the opposite end of the cell. Molecules such as insulin, immunoglobulins, and certain nutrients are transferred through the recycling endosomes by recycling and transcytosis.
IgG molecules from a mother undergo transcytosis starting around 13 weeks of gestation. The amount of IgG transferred and entering the fetal blood circulation increases with...
IgG molecules from a mother undergo transcytosis starting around 13 weeks of gestation. The amount of IgG transferred and entering the fetal blood circulation increases with...
2.8K