ADAR1 promotes systemic sclerosis via modulating classic macrophage activation.

Area of Science:

• Immunology
• Molecular Biology
• Pathology

Background:

• Systemic sclerosis (SSc) is a multisystem autoimmune disease characterized by inflammation and fibrosis.
• The precise mechanisms driving SSc pathogenesis, particularly the inflammatory response, are not fully understood.

Purpose of the Study:

• To investigate the role of adenosine deaminase acting on RNA (ADAR1) in the development of SSc.
• To explore ADAR1's function in macrophage activation and its potential as a therapeutic target.

Main Methods:

• Utilized ADAR1 heterozygous knockout (AD1+/-) and myeloid-specific ADAR1 knockout mice.
• Employed histopathological analyses and western blot to assess fibrosis and molecular changes.
• Examined the impact of ADAR1 deficiency on macrophage activation and inflammatory mediator expression.

Main Results:

• ADAR1 is highly expressed in macrophages during early bleomycin-induced SSc.
• ADAR1 deficiency in macrophages significantly reduced skin and lung fibrosis in SSc models.
• Deletion of ADAR1 inhibited macrophage activation by diminishing NF-κB signaling and reducing iNOS and IL-1β expression.

Conclusions:

• ADAR1 plays a crucial role in promoting macrophage activation during the onset of SSc.
• Targeting ADAR1 presents a potential novel therapeutic strategy for managing SSc and related fibrotic conditions.