Journal
JOURNAL OF CELLULAR PHYSIOLOGY
Volume 236, Issue 11, Pages 7554-7564Publisher
WILEY
DOI: 10.1002/jcp.30396
Keywords
antigen presentation; antigen processing; dendritic cell; Moyamoya disease; RNF213
Categories
Funding
- Japan Agency for Medical Research and Development [J170001344]
- Ministry of Health, Labour and Welfare [S17310031]
- Japan Society for the Promotion of Science [17K10815, 20K09362]
- Gonryo Medical Foundation
- Grants-in-Aid for Scientific Research [20K09362] Funding Source: KAKEN
Ask authors/readers for more resources
The study found that RNF213 plays a critical role in antigen uptake, processing, and presentation, with Rnf213-KO and Rnf213-KI mice experiments showing that RNF213 deficiency leads to decreased antigen uptake and processing capabilities, resulting in the inability to effectively activate antigen-specific T cells.
Growing evidence suggest the association between Moyamoya disease (MMD) and immune systems, such as antigen presenting cells in particular. Rnf213 gene, a susceptibility gene for MMD, is highly expressed in immune tissues, however, its function remains unclear. In addition, the physiological role of RNF213 gene polymorphism c.14576G > A (rs112735431), susceptibility variant for MMD, is also poorly understood. By studying Rnf213-knockout (Rnf213-KO) mice with deletion of largest exon32 and Rnf213-knockin (Rnf213-KI) mice with insertion of single-nucleotide polymorphism corresponding to c.14576G > A mutation in MMD patients, we aimed to investigate the role of RNF213 in dendritic cell development, and antigen processing and presentation. First, we found a high level of Rnf213 gene expression in conventional DCs and monocytes. Second, flow cytometric and confocal microscopic analysis revealed ovalbumin protein-pulsed Rnf213-KO and Rnf213-KI DCs showed impaired antigen uptake, proteolysis and reduced numbers of endosomes and lysosomes, and thereby failed to activate and proliferate antigen-specific T cells efficiently. In addition, Rnf213-KI DCs showed a similar phenotype to that of Rnf213-KO BMDCs. In conclusion, our findings suggest the critical role of RNF213 in antigen uptake, processing and presentation.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available