한빛사논문
- 조회214
So-Young Kim 1†, June-Young Koh 1,2†, Dong Hyeon Lee 3†, Hyung-Don Kim 1, Seong Jin Choi 1, Yun Yeong Ko 4, Ha Seok Lee 1, Jeong Seok Lee 1,2, In Ah Choi 5, Eun Young Lee 6, Hye Won Jeong 5, Min Kyung Jung 4, Su-Hyung Park 1, Jun Yong Park 7, Won Kim 3, Eui-Cheol Shin 1,4
1Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea
2GENOME INSIGHT Inc., Daejeon 34051, Republic of Korea
3Department of Internal Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul National University College of Medicine, Seoul 07061, Republic of Korea
4The Center for Viral Immunology, Korea Virus Research Institute, Institute for Basic Science (IBS), Daejeon 34126, Republic of Korea
5Department of Internal Medicine, Chungbuk National University College of Medicine, Cheongju 28644, Republic of Korea
6Division of Rheumatology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul 03080, Republic of Korea
7Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
†These authors contributed equally to this work.
Corresponding authors: Jun Yong Park, Won Kim, Eui-Cheol Shin
Abstract
Background & aims: Chronic hepatitis C virus (HCV) infection results in abnormal immunological alterations, which are not fully normalized after viral elimination by direct-acting antiviral (DAA) treatment. Here we longitudinally examined phenotypic, transcriptomic, and epigenetic alterations in peripheral blood regulatory T (TREG) cells from patients with chronic HCV infection according to DAA treatment.
Methods: Patients with chronic genotype 1b HCV infection who achieved sustained virologic response (SVR) by DAA treatment and age-matched healthy donors were recruited. Phenotypic characteristics of TREG cells were investigated through flow cytometry analysis. Moreover, transcriptomic and epigenetic landscape of TREG cells were analyzed using RNA-seq and ATAC-seq analysis.
Results: The TREG cell population-especially the activated TREG cell subpopulation-was expanded in peripheral blood during chronic HCV infection, and this expansion was sustained even after viral clearance. RNA-seq analysis revealed that viral clearance did not abrogate the inflammatory features of these TREG cells, such as TREG activation and TNF signal. Moreover, ATAC-seq analysis showed inflammatory imprinting in the epigenetic landscape of TREG cells from patients, which remained after treatment. These findings were further confirmed by intracellular cytokine staining, demonstrating that TREG cells exhibited inflammatory features and TNF production in chronic HCV infection that were maintained after viral clearance.
Conclusions: Overall, our results showed that during chronic HCV infection, the expanded TREG cell population acquired inflammatory features at phenotypic, transcriptomic, and epigenetic levels, which were maintained even after successful viral elimination by DAA treatment. Further studies are warranted to examine the clinical significance of sustained inflammatory features in the TREG cell population after recovery from chronic HCV infection.
Impact and implications: During chronic HCV infection, several immune components are altered both quantitatively and qualitatively. The recent introduction of DAAs led to a high cure rate of chronic HCV infection. Nevertheless, we have demonstrated that inflammatory features of TREG cells are maintained at phenotypic, transcriptomic, and epigenetic levels even after successful DAA treatment. Further in-depth studies are required to investigate the long-term clinical outcomes of patients who have recovered from chronic HCV infection.
논문정보
- Research article
- 2024년 06월 (BRIC 등록일 2024-06-17)
- 국내 연구진
- 의약학 > 면역의학
관련 보도자료
- Bio통신원
- 2024. 07. 09
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