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Intranuclear delivery of the transcription modulation domain of Tbet-improved lupus nephritis in (NZB/NZW) F1 lupus-prone mice

Authors
 Jae-Seung Moon  ;  Chin Hee Mun  ;  Jung-Ho Kim  ;  Jen-Young Cho  ;  Sung-Dong Park  ;  Tae-Yoon Park  ;  Jin-Su Shin  ;  Chun-Chang Ho  ;  Yong-Beom Park  ;  Sankar Ghosh  ;  Alfred L M Bothwell  ;  Sang-Won Lee  ;  Sang-Kyou Lee 
Citation
 Kidney International, Vol.93(5) : 1118-1130, 2018 
Journal Title
 Kidney International 
ISSN
 0085-2538 
Issue Date
2018
Keywords
T helper 1 cells ; Tbet ; Treg cells ; inflammatory microenvironment ; nucleus-transducible form ; systemic lupus erythematosus
Abstract
Excessive expression of Tbet and IFNgamma is evidence of systemic lupus erythematosus (SLE) in lupus patients. In this study, the nucleus-transducible form of Transcription Modulation Domain (TMD) of Tbet (ntTbet-TMD), which is a fusion protein between Protein Transduction Domain Hph-1 (Hph-1-PTD) and the TMD of Tbet comprising DNA binding domain and isotype-specific domain, was generated to inhibit Tbet-mediated transcription in the interactomic manner. ntTbet-TMD was effectively delivered into the nucleus of the cells and specifically inhibited Tbet-mediated transcription without influencing the differentiation of other T cell subsets and signaling events for T cell activation. The severity of nephritis was significantly reduced by ntTbet-TMD as effectively as methylprednisolone in lupus-prone mice. The number of Th1, Th2 or Th17 cells and the secretion of their cytokines substantially decreased in the spleen and kidney of lupus-prone mice by ntTbet-TMD treatment. In contrast to methylprednisolone, the marked increase of Treg cells and the secretion of their immunosuppressive cytokine were detected in the spleen of (NZB/NZW) F1 mice treated with ntTbet-TMD. Thus, ntTbet-TMD can improve nephritis in lupus-prone mice by modulating the overall proinflammatory microenvironment and rebalancing T cell subsets, leading to new immune therapeutics for Th1-mediated autoimmune diseases.
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/162277
Full Text
https://www.sciencedirect.com/science/article/pii/S0085253817308530
DOI
10.1016/j.kint.2017.11.017
Appears in Collections:
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실)
Yonsei Authors
박용범(Park, Yong Beom)
이상원(Lee, Sang Won)
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