Interactomic inhibition of Eomes in the nucleus alleviates EAE via blocking the conversion of Th17 cells into non-classic Th1 cells. Issue 2 (3rd April 2022)

• Record Type: Journal Article
• Authors: Shin, Bo-Young; Lee, Su-Hyeon; Kim, Yuna; An, Jaekyeung; Park, Tae-Yoon; Lee, Sang-Kyou
• Is Part Of: Immunological medicine. Volume 45:Issue 2(2022)
• Page Start: 119
• Page End: 127
• Publication Date: 2022-04-03
• Subjects: Th17 -- non-classic Th1 -- experimental autoimmune encephalomyelitis -- T-cell subset differentiation -- intranuclear delivery of the protein; Immune System Phenomena; Immune System Diseases; Immunology -- Periodicals; Immunology; Periodical; Periodicals; Electronic journals; 571.96
• DOI: 10.1080/25785826.2022.2031812
• Languages: English
• ISSNs: 2578-5826

Abstract

Abstract: 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.