title: dNP2 is a blood-brain barrier-permeable peptide enabling ctCTLA-4 protein delivery to ameliorate experimental autoimmune encephalomyelitis.
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.
authors.affiliation: Department of Life Science, College of Natural Sciences, Hanyang University, Seoul 133-791, Republic of Korea.|Research Institute for Natural Sciences, Hanyang University, Seoul 133-791, Republic of Korea.
authors.forename: Sangho
authors.initials: S
authors.lastname: Lim
authors.affiliation: Department of Life Science, College of Natural Sciences, Hanyang University, Seoul 133-791, Republic of Korea.|Research Institute for Natural Sciences, Hanyang University, Seoul 133-791, Republic of Korea.
authors.forename: Won-Ju
authors.initials: WJ
authors.lastname: Kim
authors.affiliation: Department of Life Science, College of Natural Sciences, Hanyang University, Seoul 133-791, Republic of Korea.|Research Institute for Natural Sciences, Hanyang University, Seoul 133-791, Republic of Korea.
authors.forename: Yeon-Ho
authors.initials: YH
authors.lastname: Kim
authors.affiliation: Center for Neuroscience Imaging Research (CNIR), Institute for Basic Science (IBS), Suwon 440-746, Republic of Korea.|Samsung Advanced Institute for Health Sciences &Technology (SAIHST), Seoul 135-710, Republic of Korea.
authors.forename: Sohee
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Life Science, College of Natural Sciences, Hanyang University, Seoul 133-791, Republic of Korea.|Research Institute for Natural Sciences, Hanyang University, Seoul 133-791, Republic of Korea.
authors.forename: Ja-Hyun
authors.initials: JH
authors.lastname: Koo
authors.affiliation: Department of Life Science, College of Natural Sciences, Hanyang University, Seoul 133-791, Republic of Korea.|Research Institute for Natural Sciences, Hanyang University, Seoul 133-791, Republic of Korea.
authors.forename: Jung-Ah
authors.initials: JA
authors.lastname: Lee
authors.affiliation: Department of Life Science, College of Natural Sciences, Hanyang University, Seoul 133-791, Republic of Korea.|Research Institute for Natural Sciences, Hanyang University, Seoul 133-791, Republic of Korea.
authors.forename: Heeseok
authors.initials: H
authors.lastname: Yoon
authors.affiliation: Department of Life Science, College of Natural Sciences, Hanyang University, Seoul 133-791, Republic of Korea.|Research Institute for Natural Sciences, Hanyang University, Seoul 133-791, Republic of Korea.
authors.forename: Do-Hyun
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Department of Life Science, College of Natural Sciences, Hanyang University, Seoul 133-791, Republic of Korea.|Research Institute for Natural Sciences, Hanyang University, Seoul 133-791, Republic of Korea.
authors.forename: Hong-Jai
authors.initials: HJ
authors.lastname: Park
authors.affiliation: Division of Integrative Bioscience and Biotechnology, Pohang University of Science and Technology, Pohang 790-784, Republic of Korea.
authors.forename: Hye-Mi
authors.initials: HM
authors.lastname: Kim
authors.affiliation: Department of Life Science, College of Natural Sciences, Hanyang University, Seoul 133-791, Republic of Korea.|Research Institute for Natural Sciences, Hanyang University, Seoul 133-791, Republic of Korea.
authors.forename: Hong-Gyun
authors.initials: HG
authors.lastname: Lee
authors.affiliation: Department of Life Science, College of Natural Sciences, Hanyang University, Seoul 133-791, Republic of Korea.|Research Institute for Natural Sciences, Hanyang University, Seoul 133-791, Republic of Korea.
authors.forename: Ji
authors.initials: J
authors.lastname: Yun Kim
authors.affiliation: Department of Life Science, College of Natural Sciences, Hanyang University, Seoul 133-791, Republic of Korea.|Research Institute for Natural Sciences, Hanyang University, Seoul 133-791, Republic of Korea.
authors.forename: Jae-Ung
authors.initials: JU
authors.lastname: Lee
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
authors.forename: Jae
authors.initials: J
authors.lastname: Hun Shin
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
authors.forename: Lark
authors.initials: L
authors.lastname: Kyun Kim
authors.affiliation: Department of Mechanical Engineering, School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology, Pohang 790-784, Republic of Korea.
authors.forename: Junsang
authors.initials: J
authors.lastname: Doh
authors.affiliation: Center for Neuroscience Imaging Research (CNIR), Institute for Basic Science (IBS), Suwon 440-746, Republic of Korea.|Department of Biological Science, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Hongtae
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea.
authors.forename: Sang-Kyou
authors.initials: SK
authors.lastname: Lee
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
authors.forename: Alfred L M
authors.initials: ALM
authors.lastname: Bothwell
authors.affiliation: Center for Neuroscience Imaging Research (CNIR), Institute for Basic Science (IBS), Suwon 440-746, Republic of Korea.|Samsung Advanced Institute for Health Sciences &Technology (SAIHST), Seoul 135-710, Republic of Korea.|Department of Biological Science, Sungkyunkwan University, Suwon 440-746, Republic of Korea.|Department of Biomedical Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Minah
authors.initials: M
authors.lastname: Suh
authors.affiliation: Department of Life Science, College of Natural Sciences, Hanyang University, Seoul 133-791, Republic of Korea.|Research Institute for Natural Sciences, Hanyang University, Seoul 133-791, Republic of Korea.|Center for Neuroscience Imaging Research (CNIR), Institute for Basic Science (IBS), Suwon 440-746, Republic of Korea.
authors.forename: Je-Min
authors.initials: JM
authors.lastname: Choi
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism*; D060908:CTLA-4 Antigen / Q000276:immunology*; D002352:Carrier Proteins / Q000378:metabolism*; D057846:Cell-Penetrating Peptides / Q000378:metabolism*; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D006367:HeLa Cells; D006801:Humans; D066298:In Vitro Techniques; D019169:Jurkat Cells; D051379:Mice; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism
chemical_list: D060908:CTLA-4 Antigen; D002352:Carrier Proteins; D057846:Cell-Penetrating Peptides; D010446:Peptide Fragments; C000606975:dNP2 peptide; D044767:Ubiquitin-Protein Ligases; C587954:UFL1 protein, human