한빛사논문
- 조회558
Jin-Sil Park1, SeungCheon Yang1, Sun-Hee Hwang1, JeongWon Choi1, Seung-Ki Kwok12, Young-Yun Kong3, Jeehee Youn4, Mi-La Cho#156, Sung-Hwan Park#12
1The Rheumatism Research Center, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
2Divison of Rheumatology, Department of Internal Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
3School of Biological Sciences, Seoul National University, Seoul, Republic of Korea.
4Laboratory of Autoimmunology, Department of Anatomy and Cell Biology, College of Medicine, Hanyang University, Seoul, 04763, Korea.
5Department of Medical Lifescience, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
6Department of Biomedicine & Health Sciences, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
#Contributed equally.
Abstract
Objective
CR6-interacting factor 1 (Crif1) is a nuclear transcriptional regulator and a mitochondrial inner membrane protein; however, its functions in B lymphocytes have been poorly defined. In this study, we investigated the effects of Crif1 on B-cell metabolic regulation, cell function, and autoimmune diseases.
Methods
Using mice with B cell-specific deletion of Crif1 (Crif1ΔCD19), we assessed the relevance of Crif1 function for lupus disease parameters including anti-double-stranded DNA, cytokines, and kidney pathology. RNA sequencing was performed on B cells from Crif1ΔCD19 mice. The phenotypic and metabolic changes in immune cells were evaluated in Crif1ΔCD19 mice. Roquinsan/+ mice crossed with Crif1ΔCD19 mice were monitored to assess the functionality of Crif1-deficient B cells in lupus development.
Results
Crif1ΔCD19 mice showed an autoimmune lupus-like phenotype, including high levels of autoantibodies to double-stranded DNA and severe lupus nephritis with increased mesangial hypercellularity. While loss of Crif1 in B cells showed impaired mitochondrial oxidative function, Crif1-deficient B cells promoted the production of IL-17 and IL-6 and was more potent in helping T cells develop into T follicular helper cells. In an autoimmune lupus mouse model, depletion of Crif1 in B cells exacerbated lupus severity and Crif1 overexpression prevented lupus development in Roquinsan/san mice.
Conclusion
These results showed that Crif1 was negatively correlated with disease severity, and overexpression of Crif1 ameliorated disease development. Our findings suggest that Crif1 is essential for preventing lupus development by maintaining B cell self-tolerance.
논문정보
- Research article
- 2022년 02월 (BRIC 등록일 2022-04-07)
- 국내 연구진
- 생명과학 > 면역학
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