The Cysteine-Containing Cell-Penetrating Peptide AP Enables Efficient Macromolecule Delivery to T Cells and Controls Autoimmune Encephalomyelitisopen access
- Authors
- Kim, Won-Ju; Kim, Gil-Ran; Cho, Hyun-Jung; Choi, Je-Min
- Issue Date
- Aug-2021
- Publisher
- MDPI
- Keywords
- T cell; immune regulation; cell-penetrating peptide; AP; CTLA-4; multiple sclerosis; experimental autoimmune encephalomyelitis EAE; drug delivery system
- Citation
- PHARMACEUTICS, v.13, no.8, pp.1 - 16
- Indexed
- SCIE
SCOPUS
- Journal Title
- PHARMACEUTICS
- Volume
- 13
- Number
- 8
- Start Page
- 1
- End Page
- 16
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/141396
- DOI
- 10.3390/pharmaceutics13081134
- ISSN
- 1999-4923
- Abstract
- T cells are key immune cells involved in the pathogenesis of several diseases, rendering them important therapeutic targets. Although drug delivery to T cells is the subject of continuous research, it remains challenging to deliver drugs to primary T cells. Here, we used a peptide-based drug delivery system, AP, which was previously developed as a transdermal delivery peptide, to modulate T cell function. We first identified that AP-conjugated enhanced green fluorescent protein (EGFP) was efficiently delivered to non-phagocytic human T cells. We also confirmed that a nine-amino acid sequence with one cysteine residue was the optimal sequence for protein delivery to T cells. Next, we identified the biodistribution of AP-dTomato protein in vivo after systemic administration, and transduced it to various tissues, such as the spleen, liver, intestines, and even to the brain across the blood-brain barrier. Next, to confirm AP-based T cell regulation, we synthesized the AP-conjugated cytoplasmic domain of CTLA-4, AP-ctCTLA-4 peptide. AP-ctCTLA-4 reduced IL-17A expression under Th17 differentiation conditions in vitro and ameliorated experimental autoimmune encephalomyelitis, with decreased numbers of pathogenic IL-17A(+)GM-CSF+ CD4 T cells. These results collectively suggest the AP peptide can be used for the successful intracellular regulation of T cell function, especially in the CNS.
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