LRR domain of NLRX1 protein delivery by dNP2 inhibits T cell functions and alleviates autoimmune encephalomyelitis
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Koo, Ja-Hyun | - |
dc.contributor.author | Kim, Do-Hyun | - |
dc.contributor.author | Cha, Donghun | - |
dc.contributor.author | Kang, Min-Jong | - |
dc.contributor.author | Choi, Je-Min | - |
dc.date.accessioned | 2021-08-02T09:53:20Z | - |
dc.date.available | 2021-08-02T09:53:20Z | - |
dc.date.created | 2021-05-12 | - |
dc.date.issued | 2020-02 | - |
dc.identifier.issn | 1838-7640 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/10732 | - |
dc.description.abstract | Multiple sclerosis (MS) is a demyelinating inflammatory disease of the central nervous system (CNS), which is a chronic progressive disease and is caused by uncontrolled activation of myelin antigen specific T cells. It has high unmet medical needs due to the difficulty of efficient drug delivery into the CNS to control tissue inflammation. In this study, we demonstrate that a fusion protein of NOD-like receptor family member X1 (NLRX1) and blood brain barrier (BBB)-permeable peptide, dNP2 ameliorates experimental autoimmune encephalomyelitis (EAE). Methods: We purified recombinant LRR or NBD regions of NLRX1 protein conjugated with dNP2. To examine intracellular delivery efficiency of the recombinant protein, we incubated the proteins with Jurkat T cells or murine splenic T cells and their delivery efficiency was analyzed by flow cytometry. To investigate the therapeutic efficacy in an EAE model, we injected the recombinant protein into mice with 3 different treatment schemes e.g., prevention, semi-therapeutic, and therapeutic. To analyze their functional roles in T cells, we treated MACS-sorted naive CD4 T cells with the proteins during their activation and differentiation into Th1, Th17, and Treg cells. Results: dNP2-LRR protein treatment showed significantly higher delivery efficiency than TAT-LRR or LRR alone in Jurkat T cells and mouse splenic T cells. In all three treatment schemes of EAE experiments, dNP2-LRR administration showed ameliorated tissue inflammation and disease severity with reduced number of infiltrating T cells producing inflammatory cytokines such as IFN gamma. In addition, dNP2-LRR inhibited T cell activation, cytokine production, and Th1 differentiation. Conclusion: These results suggest that dNP2-LRR is a novel agent, which regulates effector T cell functions and could be a promising molecule for the treatment of CNS autoimmune diseases such as multiple sclerosis. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | IVYSPRING INT PUBL | - |
dc.title | LRR domain of NLRX1 protein delivery by dNP2 inhibits T cell functions and alleviates autoimmune encephalomyelitis | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Choi, Je-Min | - |
dc.identifier.doi | 10.7150/thno.43441 | - |
dc.identifier.scopusid | 2-s2.0-85080926795 | - |
dc.identifier.wosid | 000514452800018 | - |
dc.identifier.bibliographicCitation | THERANOSTICS, v.10, no.7, pp.3138 - 3150 | - |
dc.relation.isPartOf | THERANOSTICS | - |
dc.citation.title | THERANOSTICS | - |
dc.citation.volume | 10 | - |
dc.citation.number | 7 | - |
dc.citation.startPage | 3138 | - |
dc.citation.endPage | 3150 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.isOpenAccess | Y | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Research & Experimental Medicine | - |
dc.relation.journalWebOfScienceCategory | Medicine, Research & Experimental | - |
dc.subject.keywordPlus | BLOOD-BRAIN-BARRIER | - |
dc.subject.keywordPlus | MULTIPLE-SCLEROSIS | - |
dc.subject.keywordPlus | PEPTIDE | - |
dc.subject.keywordPlus | DISEASE | - |
dc.subject.keywordPlus | ENTRY | - |
dc.subject.keywordPlus | PROTEOGLYCANS | - |
dc.subject.keywordPlus | INTERFERON | - |
dc.subject.keywordPlus | ENDOTOXIN | - |
dc.subject.keywordPlus | REMOVAL | - |
dc.subject.keywordAuthor | NOD-like receptor family member X1 | - |
dc.subject.keywordAuthor | T cell | - |
dc.subject.keywordAuthor | BBB-penetrating peptide | - |
dc.subject.keywordAuthor | dNP2 | - |
dc.subject.keywordAuthor | experimental autoimmune encephalomyelitis | - |
dc.identifier.url | https://www.thno.org/v10p3138.htm | - |
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.
222, Wangsimni-ro, Seongdong-gu, Seoul, 04763, Korea+82-2-2220-1365
COPYRIGHT © 2021 HANYANG UNIVERSITY.
Certain data included herein are derived from the © Web of Science of Clarivate Analytics. All rights reserved.
You may not copy or re-distribute this material in whole or in part without the prior written consent of Clarivate Analytics.