Chromatin accessibility landscapes of immune cells in rheumatoid arthritis nominate monocytes in disease pathogenesis.
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
Here, we analysed the genome-wide active DNA regulatory elements of four major immune cells, namely monocytes, B cells, CD4+ T cells and CD8+ 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.
['Zong|Dandan|D|', 'Huang|Beibei|B|', 'Li|Young|Y|', 'Lu|Yichen|Y|', 'Xiang|Nan|N|', 'Guo|Chuang|C|', 'Liu|Qian|Q|', 'Sha|Qing|Q|', 'Du|Pengcheng|P|', 'Yu|Qiaoni|Q|', 'Zhang|Wen|W|', 'Cai|Pengfei|P|', 'Sun|Yanping|Y|', 'Tao|Jinhui|J|', 'Li|Xiaomei|X|', 'Cai|Shanbao|S|', 'Qu|Kun|K|0000-0002-5555-8437']
Monocytes Rheumatoid arthritis (RA) Chromatin dysregulation C-reactive protein FRA2