Interactomic inhibition of Eomes in the nucleus alleviates EAE via blocking the conversion of Th17 cells into non-classic Th1 cells

Bo Young Shin, Su Hyeon Lee, Yuna Kim, Jaekyeung An, Tae Yoon Park, Sang Kyou Lee

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)


Th17 cells are implicated in the pathogenesis of several autoimmune diseases. During the inflammation, Th17 cells exposed to IL-12 can shift towards the Th1 phenotype. These shifted cells are defined as ‘non-classic Th1 cells’. Th17-derived non-classic Th1 cells play a critical role in late-onset chronic inflammatory diseases and are more pathogenic than the unshifted Th17 cells. Eomes is a transcription factor highly expressed in non-classic Th1 cells. To study the functional role of Eomes without genetic alteration, novel recombinant protein, ntEomes-TMD, was generated by fusing TMD of Eomes and Hph-1-PTD that facilitate intracellular delivery of its cargo molecule. ntEomes-TMD was delivered into the nucleus of the cells without influencing the T cell activation and cytotoxicity. ntEomes-TMD specifically inhibited the Eomes- and ROR-γt-mediated transcription and suppressed the Th1 and Th17 differentiation. Interestingly, ntEomes-TMD blocked the generation of non-classic Th1 cells from Th17 cells, leading to the inhibition of IFN-γ and GM-CSF secretion. In EAE, ntEomes-TMD alleviated the symptoms of EAE, and the combination treatment using ntEomes-TMD and anti-IL-17 mAb together showed better therapeutic efficacy than anti-IL-17 mAb treatment. The results suggest that ntEomes-TMD can be a new therapeutic reagent for treating chronic inflammatory diseases associated with non-classic Th1 cells.

Original languageEnglish
Pages (from-to)119-127
Number of pages9
JournalImmunological Medicine
Issue number2
Publication statusPublished - 2022

Bibliographical note

Funding Information:
This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) [grant number NRF-2016K1A1A2912755] and the Brain Korea 21 (BK21) PLUS Program, Republic of Korea.

Publisher Copyright:
© 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group on behalf of the Japanese Society of Clinical Immunology.

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology


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