期刊
FRONTIERS IN IMMUNOLOGY
卷 13, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2022.1051254
关键词
ADAR1; macrophage activation; systemic sclerosis; NF-kappa B; IL-1 beta
类别
资金
- Natural Science Foundation of China [82071828]
- National Institutes of Health [HL119053, HL147313]
- China Postdoctoral Science Foundation [2021M692559]
- Early Career Research Start-up Plan of Xi'an Jiaotong University, Central University Basic Research Fund [xxj032022001]
In this study, the researchers discovered that ADAR1 is abundantly expressed in macrophages in the early stage of systemic sclerosis (SSc) and plays an essential role in SSc formation and macrophage activation.
Introduction: As a multisystem autoimmune disorder disease, systemic sclerosis (SSc) is characterized by inflammation and fibrosis in the skin and other internal organs. However, mechanisms underlying the inflammatory response that drives the development of SSc remain largely unknown. Methods: ADAR1 heterozygous knockout (AD1+/-) mice and myeloid-specific ADAR1 knockout mice were used to determine the function of ADAR1 in SSc. Histopathological analyses and western blot confirmed the role of ADAR1 in bleomycin-induced increased skin and lung fibrosis. Results: In this study, we discover that adenosine deaminase acting on RNA (ADAR1), a deaminase converting adenosine to inosine (i.e., RNA editing) in RNA, is abundantly expressed in macrophages in the early stage of bleomycininduced SSc. Importantly, ADAR1 is essential for SSc formation and indispensable for classical macrophage activation because ADAR1 deficiency in macrophages significantly ameliorates skin and lung sclerosis and inhibits the expression of inflammation mediator inducible NO synthase (iNOS) and IL-1b in macrophages. Mechanistically, deletion of ADAR1 blocks macrophage activation through diminishing NF-kB signaling. Discussion: Our studies reveal that ADAR1 promotes macrophage activation in the onset of SSc. Thus, targeting ADAR1 could be a potential novel therapeutic strategy for treating sclerosis formation.
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