dNP2 is a blood-brain barrier-permeable peptide enabling ctCTLA-4 protein delivery to ameliorate experimental autoimmune encephalomyelitis
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- Title
- dNP2 is a blood-brain barrier-permeable peptide enabling ctCTLA-4 protein delivery to ameliorate experimental autoimmune encephalomyelitis
- Authors
- Sangho Lim; Won-Ju Kim; Yeon-Ho Kim; Sohee Lee; Ja-Hyun Koo; Jung-Ah Lee; Heeseok Yoon; Do-Hyun Kim; Hong-Jai Park; Kim, HM; Hong-Gyun Lee; Ji Yun Kim; Jae-Ung Lee; Jae Hun Shin; Lark Kyun Kim; Doh, J; Hye-Mi Kim; Lee, SK; Bothwell, ALM; Suh, M; Choi, JM
- Date Issued
- 2015-09
- Publisher
- Macmillan Publishers Limited. All rights reserved
- Abstract
- Central nervous system (CNS)-infiltrating effector T cells play critical roles in the development and progression of multiple sclerosis (MS). However, current drugs for MS are very limited due to the difficulty of delivering drugs into the CNS. Here we identify a cell-permeable peptide, dNP2, which efficiently delivers proteins into mouse and human T cells, as well as various tissues. Moreover, it enters the brain tissue and resident cells through blood vessels by penetrating the tightly organized blood-brain barrier. The dNP2-conjugated cytoplasmic domain of cytotoxic T-lymphocyte antigen 4 (dNP2-ctCTLA-4) negatively regulates activated T cells and shows inhibitory effects on experimental autoimmune encephalomyelitis in both preventive and therapeutic mouse models, resulting in the reduction of demyelination and CNS-infiltrating T helper 1 and T helper 17 cells. Thus, this study demonstrates that dNP2 is a blood-brain barrier-permeable peptide and dNP2-ctCTLA-4 could be an effective agent for treating CNS inflammatory diseases such as MS.
- Keywords
- cytoplasmic domain of cytotoxic T lymphocyte antigen 4; cytotoxic T lymphocyte antigen 4; neuroprotective agent; peptide derivative; recombinant dNP2; recombinant protein; unclassified drug; blood; cytology; cytoplasm; drug; experimental study; immune response; peptide; permeability; protein; rodent; animal cell; animal experiment; animal model; Article; blood brain barrier; CD4+ T lymphocyte; cell permeabilization; central nervous system; confocal microscopy; controlled study; demyelination; drug conjugation; drug penetration; experimental autoimmune encephalomyelitis; female; fluorescence microscopy; HeLa cell line; human; human cell; inflammatory disease; mouse; mouse model; multiple sclerosis; neuroprotection; nonhuman; T lymphocyte; tandem repeat; Th1 cell; Th17 cell
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/13458
- DOI
- 10.1038/NCOMMS9244
- ISSN
- 2041-1723
- Article Type
- Article
- Citation
- NATURE COMMUNICATIONS, vol. 6, page. 8244, 2015-09
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