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,
Jinhui Tao,
Xiaomei Li,
Shanbao Cai,
Kun Qu
Affiliations
Dandan Zong
Department of Rheumatology and Immunology, The First Affiliated Hospital of USTC, Division of Molecular Medicine, Hefei National Laboratory for Physical Sciences at Microscale, Division of Life Sciences and Medicine, University of Science and Technology of China
Beibei Huang
Department of Rheumatology and Immunology, The First Affiliated Hospital of USTC, Division of Molecular Medicine, Hefei National Laboratory for Physical Sciences at Microscale, Division of Life Sciences and Medicine, University of Science and Technology of China
Young Li
Department of Rheumatology and Immunology, The First Affiliated Hospital of USTC, Division of Molecular Medicine, Hefei National Laboratory for Physical Sciences at Microscale, Division of Life Sciences and Medicine, University of Science and Technology of China
Yichen Lu
Department of Rheumatology and Immunology, The First Affiliated Hospital of USTC, Division of Molecular Medicine, Hefei National Laboratory for Physical Sciences at Microscale, Division of Life Sciences and Medicine, University of Science and Technology of China
Nan Xiang
Department of Rheumatology and Immunology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China
Chuang Guo
Department of Rheumatology and Immunology, The First Affiliated Hospital of USTC, Division of Molecular Medicine, Hefei National Laboratory for Physical Sciences at Microscale, Division of Life Sciences and Medicine, University of Science and Technology of China
Qian Liu
Department of Rheumatology and Immunology, The First Affiliated Hospital of USTC, Division of Molecular Medicine, Hefei National Laboratory for Physical Sciences at Microscale, Division of Life Sciences and Medicine, University of Science and Technology of China
Qing Sha
Department of Rheumatology and Immunology, The First Affiliated Hospital of USTC, Division of Molecular Medicine, Hefei National Laboratory for Physical Sciences at Microscale, Division of Life Sciences and Medicine, University of Science and Technology of China
Pengcheng Du
Department of Rheumatology and Immunology, The First Affiliated Hospital of USTC, Division of Molecular Medicine, Hefei National Laboratory for Physical Sciences at Microscale, Division of Life Sciences and Medicine, University of Science and Technology of China
Qiaoni Yu
Department of Rheumatology and Immunology, The First Affiliated Hospital of USTC, Division of Molecular Medicine, Hefei National Laboratory for Physical Sciences at Microscale, Division of Life Sciences and Medicine, University of Science and Technology of China
Wen Zhang
Department of Rheumatology and Immunology, The First Affiliated Hospital of USTC, Division of Molecular Medicine, Hefei National Laboratory for Physical Sciences at Microscale, Division of Life Sciences and Medicine, University of Science and Technology of China
Pengfei Cai
Department of Rheumatology and Immunology, The First Affiliated Hospital of USTC, Division of Molecular Medicine, Hefei National Laboratory for Physical Sciences at Microscale, Division of Life Sciences and Medicine, University of Science and Technology of China
Yanping Sun
Department of Rheumatology and Immunology, The First Affiliated Hospital of USTC, Division of Molecular Medicine, Hefei National Laboratory for Physical Sciences at Microscale, Division of Life Sciences and Medicine, University of Science and Technology of China
Jinhui Tao
Department of Rheumatology and Immunology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China
Xiaomei Li
Department of Rheumatology and Immunology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China
Shanbao Cai
Department of Orthopaedics and Bone Oncology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China
Kun Qu
Department of Rheumatology and Immunology, The First Affiliated Hospital of USTC, Division of Molecular Medicine, Hefei National Laboratory for Physical Sciences at Microscale, Division of Life Sciences and Medicine, University of Science and Technology of China
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 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.
