International Journal of Hematology

, Volume 108, Issue 4, pp 375–383 | Cite as

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
Original Article


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.


BAF complex T cell activation Immunosuppression Protein degradation Inflammation 



Nucleus-transducible BAF57-without proline-rich and HMG domain



This work was partially supported by the research grant from Good T Cells; the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No. NRF-2017R1A2A1A17069807); Global Research Laboratory (GRL) Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (NRF-2016K1A1A2912755). In addition, this work was supported in part by the Yonsei University Future-leading Research Initiative of 2015 (RMS2 2017-22-0137). We would like to thank Jee-Sang Yoon for technical assistance.

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

Supplementary material

12185_2018_2491_MOESM1_ESM.docx (597 kb)
Supplementary material 1 (DOCX 597 KB)


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Copyright information

© The Japanese Society of Hematology 2018

Authors and Affiliations

  1. 1.Department of BiotechnologyYonsei University College of Life Science and BiotechnologySeoulRepublic of Korea
  2. 2.Department of Microbiology and ImmunologyColumbia University, College of Physicians and SurgeonsNew YorkUSA
  3. 3.Good T cells, IncSeoulRepublic of Korea

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