Nature Communications (Jul 2023)
Age-related self-DNA accumulation may accelerate arthritis in rats and in human rheumatoid arthritis
- Wei-Dan Luo,
- Yu-Ping Wang,
- Jun Lv,
- Yong Liu,
- Yuan-Qing Qu,
- Xiong-Fei Xu,
- Li-Jun Yang,
- Zi-Cong Lin,
- Lin-Na Wang,
- Rui-Hong Chen,
- Jiu-Jie Yang,
- Ya-Ling Zeng,
- Rui-Long Zhang,
- Bai-Xiong Huang,
- Xiao-Yun Yun,
- Xuan-Ying Wang,
- Lin-Lin Song,
- Jian-Hui Wu,
- Xing-Xia Wang,
- Xi Chen,
- Wei Zhang,
- Hui-Miao Wang,
- Li-Qun Qu,
- Meng-Han Liu,
- Liang Liu,
- Betty Yuen Kwan Law,
- Vincent Kam Wai Wong
Affiliations
- Wei-Dan Luo
- Dr. Neher’s Biophysics Laboratory for Innovative Drug Discovery, Macau University of Science and Technology
- Yu-Ping Wang
- Dr. Neher’s Biophysics Laboratory for Innovative Drug Discovery, Macau University of Science and Technology
- Jun Lv
- The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Southwest Medical University
- Yong Liu
- The Affiliated Hospital of Southwest Medical University, Southwest Medical University
- Yuan-Qing Qu
- Dr. Neher’s Biophysics Laboratory for Innovative Drug Discovery, Macau University of Science and Technology
- Xiong-Fei Xu
- Dr. Neher’s Biophysics Laboratory for Innovative Drug Discovery, Macau University of Science and Technology
- Li-Jun Yang
- Dr. Neher’s Biophysics Laboratory for Innovative Drug Discovery, Macau University of Science and Technology
- Zi-Cong Lin
- Dr. Neher’s Biophysics Laboratory for Innovative Drug Discovery, Macau University of Science and Technology
- Lin-Na Wang
- Dr. Neher’s Biophysics Laboratory for Innovative Drug Discovery, Macau University of Science and Technology
- Rui-Hong Chen
- Dr. Neher’s Biophysics Laboratory for Innovative Drug Discovery, Macau University of Science and Technology
- Jiu-Jie Yang
- Dr. Neher’s Biophysics Laboratory for Innovative Drug Discovery, Macau University of Science and Technology
- Ya-Ling Zeng
- Dr. Neher’s Biophysics Laboratory for Innovative Drug Discovery, Macau University of Science and Technology
- Rui-Long Zhang
- Dr. Neher’s Biophysics Laboratory for Innovative Drug Discovery, Macau University of Science and Technology
- Bai-Xiong Huang
- Dr. Neher’s Biophysics Laboratory for Innovative Drug Discovery, Macau University of Science and Technology
- Xiao-Yun Yun
- Dr. Neher’s Biophysics Laboratory for Innovative Drug Discovery, Macau University of Science and Technology
- Xuan-Ying Wang
- Dr. Neher’s Biophysics Laboratory for Innovative Drug Discovery, Macau University of Science and Technology
- Lin-Lin Song
- Dr. Neher’s Biophysics Laboratory for Innovative Drug Discovery, Macau University of Science and Technology
- Jian-Hui Wu
- Dr. Neher’s Biophysics Laboratory for Innovative Drug Discovery, Macau University of Science and Technology
- Xing-Xia Wang
- Dr. Neher’s Biophysics Laboratory for Innovative Drug Discovery, Macau University of Science and Technology
- Xi Chen
- Dr. Neher’s Biophysics Laboratory for Innovative Drug Discovery, Macau University of Science and Technology
- Wei Zhang
- Dr. Neher’s Biophysics Laboratory for Innovative Drug Discovery, Macau University of Science and Technology
- Hui-Miao Wang
- Dr. Neher’s Biophysics Laboratory for Innovative Drug Discovery, Macau University of Science and Technology
- Li-Qun Qu
- Dr. Neher’s Biophysics Laboratory for Innovative Drug Discovery, Macau University of Science and Technology
- Meng-Han Liu
- Dr. Neher’s Biophysics Laboratory for Innovative Drug Discovery, Macau University of Science and Technology
- Liang Liu
- State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology
- Betty Yuen Kwan Law
- Dr. Neher’s Biophysics Laboratory for Innovative Drug Discovery, Macau University of Science and Technology
- Vincent Kam Wai Wong
- Dr. Neher’s Biophysics Laboratory for Innovative Drug Discovery, Macau University of Science and Technology
- DOI
- https://doi.org/10.1038/s41467-023-40113-3
- Journal volume & issue
-
Vol. 14,
no. 1
pp. 1 – 17
Abstract
Abstract The incidence of rheumatoid arthritis (RA) is increasing with age. DNA fragments is known to accumulate in certain autoimmune diseases, but the mechanistic relationship among ageing, DNA fragments and RA pathogenesis remain unexplored. Here we show that the accumulation of DNA fragments, increasing with age and regulated by the exonuclease TREX1, promotes abnormal activation of the immune system in an adjuvant‐induced arthritis (AIA) rat model. Local overexpression of TREX1 suppresses synovial inflammation in rats, while conditional genomic deletion of TREX1 in AIA rats result in higher levels of circulating free (cf) DNA and hence abnormal immune activation, leading to more severe symptoms. The dysregulation of the heterodimeric transcription factor AP-1, formed by c-Jun and c-Fos, appear to regulate both TREX1 expression and SASP induction. Thus, our results confirm that DNA fragments are inflammatory mediators, and TREX1, downstream of AP-1, may serve as regulator of cellular immunity in health and in RA.
