Sangho Lim1,2,*, Won-Ju Kim1,2,*, Yeon-Ho Kim1,2, Sohee Lee3,4, Ja-Hyun Koo1,2, Jung-Ah Lee1,2, Heeseok Yoon1,2, Do-Hyun Kim1,2, Hong-Jai Park1,2, Hye-Mi Kim5, Hong-Gyun Lee1,2, Ji Yun Kim1,2, Jae-Ung Lee1,2, Jae Hun Shin6, Lark Kyun Kim6, Junsang Doh7, Hongtae Kim3,8, Sang-Kyou Lee9, Alfred L.M. Bothwell6, Minah Suh3,4,8,10 & Je-Min Choi1,2,3
1Department of Life Science, College of Natural Sciences, Hanyang University, Seoul 133-791, Republic of Korea. 2 Research Institute for Natural Sciences, Hanyang University, Seoul 133-791, Republic of Korea. 3Center for Neuroscience Imaging Research (CNIR), Institute for Basic Science (IBS), Suwon 440-746, Republic of Korea. 4 Samsung Advanced Institute for Health Sciences & Technology (SAIHST), Seoul 135-710, Republic of Korea. 5Division of Integrative Bioscience and Biotechnology, Pohang University of Science and Technology, Pohang 790-784, Republic of Korea. 6Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA. 7Department of Mechanical Engineering, School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology, Pohang 790-784, Republic of Korea. 8Department of Biological Science, Sungkyunkwan University, Suwon 440-746, Republic of Korea. 9 Department of Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea. 10 Department of Biomedical Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
* These authors contributed equally to this work.
Correspondence to : Je-Min Choi
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.