Chromatin accessibility landscapes of immune cells in rheumatoid arthritis nominate monocytes in disease pathogenesis
Dandan Zong, Beibei Huang, Young Li, Yichen Lu, Nan Xiang, Chuang Guo, Qian Liu, Qing Sha, Pengcheng Du, Qiaoni Yu, Wen Zhang, Pengfei Cai, Yanping Sun, Jin‐Hui Tao, Xiaomei Li, Shanbao Cai, Kun Qu
Abstract
BACKGROUND: Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease that involves a variety of cell types. However, how the epigenetic dysregulations of peripheral immune cells contribute to the pathogenesis of RA still remains largely unclear. RESULTS: T cells, in peripheral blood of RA patients, osteoarthritis (OA) patients and healthy donors using Assay of Transposase Accessible Chromatin with sequencing (ATAC-seq). We found a strong RA-associated chromatin dysregulation signature in monocytes, but no other examined cell types. Moreover, we found that serum C-reactive protein (CRP) can induce the RA-associated chromatin dysregulation in monocytes via in vitro experiments. And the extent of this dysregulation was regulated through the transcription factor FRA2. CONCLUSIONS: Together, our study revealed a CRP-induced pathogenic chromatin dysregulation signature in monocytes from RA patients and predicted the responsible signalling pathway as potential therapeutic targets for the disease.