Immuno-suppressive function of nucleus-transducible BAF57-ΔPH in T cell activation via degradation of endogenous BAF57

Jae Seung Moon, Hong Jai Lee, Chun Chang Ho, Jin Su Shin, Sankar Ghosh, Jung Ho Kim, Sang Kyou Lee

Research output: Contribution to journalArticle

Abstract

The BAF57 subunit, an indispensable member of the BAF complex, is functionally implicated in apoptosis, cell cycle, and T cell development through chromosomal remodeling. However, the precise roles of BAF57 in the T cell receptor (TcR)-mediated signaling pathway have not been elucidated. In this study, a nucleus-transducible form of BAF57, absent the proline-rich and HMG domains (ntBAF57-ΔPH), was generated to interfere with the interaction between BAF57 and its binding protein, BAF155. ntBAF57-ΔPH was effectively delivered into mouse CD4+ T cells in a dose- and time-dependent manner, without cellular toxicity. Inhibition of T cell activation by ntBAF57-ΔPH was mediated by its disruption of the interaction between BAF155 and BAF57, leading to the degradation of endogenous BAF57 and BAF155. This phenomenon led to alterations in gene expression similar to those associated with Ciclosporin A treatment. In vivo administration of ntBAF57-ΔPH enhanced survival rate of sepsis-induced mice and reduced the LPS-induced secretion of pro-inflammatory cytokines and the expression of endogenous BAF57. These results reveal a novel function of BAF57 as an essential regulator of T cell activation. ntBAF57-ΔPH represents a novel immune-suppressive drug candidate with potential uses in the treatment of autoimmunity and graft rejection.

Original languageEnglish
Pages (from-to)375-383
Number of pages9
JournalInternational Journal of Hematology
Volume108
Issue number4
DOIs
Publication statusPublished - 2018 Oct 1

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T-Lymphocytes
Graft Rejection
T-Cell Antigen Receptor
Autoimmunity
Proline
Cyclosporine
Sepsis
Cell Cycle
Carrier Proteins
Apoptosis
Cytokines
Gene Expression
Pharmaceutical Preparations
Pleckstrin Homology Domains

All Science Journal Classification (ASJC) codes

  • Hematology

Cite this

Moon, Jae Seung ; Lee, Hong Jai ; Ho, Chun Chang ; Shin, Jin Su ; Ghosh, Sankar ; Kim, Jung Ho ; Lee, Sang Kyou. / Immuno-suppressive function of nucleus-transducible BAF57-ΔPH in T cell activation via degradation of endogenous BAF57. In: International Journal of Hematology. 2018 ; Vol. 108, No. 4. pp. 375-383.
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abstract = "The BAF57 subunit, an indispensable member of the BAF complex, is functionally implicated in apoptosis, cell cycle, and T cell development through chromosomal remodeling. However, the precise roles of BAF57 in the T cell receptor (TcR)-mediated signaling pathway have not been elucidated. In this study, a nucleus-transducible form of BAF57, absent the proline-rich and HMG domains (ntBAF57-ΔPH), was generated to interfere with the interaction between BAF57 and its binding protein, BAF155. ntBAF57-ΔPH was effectively delivered into mouse CD4+ T cells in a dose- and time-dependent manner, without cellular toxicity. Inhibition of T cell activation by ntBAF57-ΔPH was mediated by its disruption of the interaction between BAF155 and BAF57, leading to the degradation of endogenous BAF57 and BAF155. This phenomenon led to alterations in gene expression similar to those associated with Ciclosporin A treatment. In vivo administration of ntBAF57-ΔPH enhanced survival rate of sepsis-induced mice and reduced the LPS-induced secretion of pro-inflammatory cytokines and the expression of endogenous BAF57. These results reveal a novel function of BAF57 as an essential regulator of T cell activation. ntBAF57-ΔPH represents a novel immune-suppressive drug candidate with potential uses in the treatment of autoimmunity and graft rejection.",
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Immuno-suppressive function of nucleus-transducible BAF57-ΔPH in T cell activation via degradation of endogenous BAF57. / Moon, Jae Seung; Lee, Hong Jai; Ho, Chun Chang; Shin, Jin Su; Ghosh, Sankar; Kim, Jung Ho; Lee, Sang Kyou.

In: International Journal of Hematology, Vol. 108, No. 4, 01.10.2018, p. 375-383.

Research output: Contribution to journalArticle

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T1 - Immuno-suppressive function of nucleus-transducible BAF57-ΔPH in T cell activation via degradation of endogenous BAF57

AU - Moon, Jae Seung

AU - Lee, Hong Jai

AU - Ho, Chun Chang

AU - Shin, Jin Su

AU - Ghosh, Sankar

AU - Kim, Jung Ho

AU - Lee, Sang Kyou

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