한빛사논문
- 조회533
Joo Sung Shim MD1,2,3†, Eun Jee Kim PhD2,4†, Lucy Eunju Lee MD, PhD1, Joon Ye Kim MSc2,4, Yuri Cho BSc2,4, Hanna Kim BSc1, Jieun Kim MSc1, Sung Hoon Jang BSc1, Jimin Son PhD5, Jae-Ho Cheong MD, PhD6, Aekyong Kim PhD1, Beom Jin Lim MD, PhD8, Sang-Jun Ha PhD5,∗, Jason Jungsik Song MD, PhD1,7,∗, Beom Seok Kim MD, PhD2,4,∗
1Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Korea
2Division of Nephrology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Korea
3Synapse Center, Yonsei University College of Medicine, Seoul 03722, Korea
4The Research Institute for Transplantation, Yonsei University College of Medicine, Seoul 03722, Korea
5Department of Biochemistry, Yonsei University College of Life Science & Biotechnology, Seoul 03722, Korea
6Department of Surgery, Yonsei University College of Medicine, Seoul 03722, Korea
7Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul 03722, Korea
8Department of Pathology, Yonsei University College of Medicine, Seoul 06273, Korea
†These authors contributed equally to this work as co-first authors.
Address correspondence to: Sang-Jun Ha PhD, Jason Jungsik Song MD, PhD, Beom Seok Kim MD, PhD
*These authors contributed equally to this work as co-senior authors.
Abstract
Current treatment strategies for autoimmune diseases may not sufficiently control aberrant metabolism in B-cells. To address this concern, we investigated a biguanide derivative, IM156, as a potential regulator for B-cell metabolism in vitro and in vivo on overactive B-cells stimulated by the pro-inflammatory receptor TLR-9 agonist CpG oligodeoxynucleotide, a mimic of viral/bacterial DNA. Using RNA sequencing, we analyzed the B-cell transcriptome expression, identifying the major molecular pathways affected by IM156 in vivo. We also evaluated the anti-inflammatory effects of IM156 in lupus-prone NZB/W F1 mice. CD19+B-cells exhibited higher mitochondrial mass and mitochondrial membrane potential compared to T-cells and were more susceptible to IM156-mediated oxidative phosphorylation inhibition. In vivo, IM156 inhibited mitochondrial oxidative phosphorylation, cell cycle progression, plasmablast differentiation, and activation marker levels in CpG oligodeoxynucleotide-stimulated mouse spleen B-cells. Interestingly, IM156 treatment significantly increased overall survival, reduced glomerulonephritis and inhibited B-cell activation in the NZB/W F1 mice. Thus, our data indicated that IM156 suppressed the mitochondrial membrane potentials of activated B-cells in mice, contributing to the mitigation of lupus activity. Hence, IM156 may represent a therapeutic alternative for autoimmune disease mediated by B-cell hyperactivity.
논문정보
- Research article
- 2022년 11월 (BRIC 등록일 2022-11-08)
- 국내 연구진
- 의약학 > 응용의학
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