The following is a summary of “Altered RNA Editing in Atopic Dermatitis Highlights the Role of Double-Stranded RNA for Immune Surveillance,” published in the June 2023 issue of Investigative Dermatology by Karmon et al.
In addition to the predominant type 2 inflammation, atopic dermatitis (AD) is associated with dysregulated type 1 IFNmediated response. However, little is known about the pathophysiology of this dysregulation. RNA editing from adenosine to inosine plays a crucial role in immune regulation by preventing the recognition of double-stranded RNA by MDA5 and IFN activation.
Researchers examined global adenosine-to-inosine editing in Alzheimer’s disease to determine the position that altered editing plays in the pathophysiology of this condition. Analysis of three RNA-sequencing datasets of cutaneous samples from Alzheimer’s patients revealed decreased levels of adenosine-to-inosine RNA editing. This reduction was observed globally in Alu repeats, coding genes, and specific pre-mRNA loci anticipated to generate long double-stranded RNA, the primary substrate of MDA5, leading to type I IFN activation. IFN signature genes were consistently upregulated.
In contrast, despite IFN activation, global editing was not altered in systemic lupus erythematosus and systemic sclerosis. Their findings suggest that alterations in editing that impair the innate immune response may be implicated in the pathogenesis of Alzheimer’s disease. It may apply to additional autoimmune and inflammatory conditions.
Source: sciencedirect.com/science/article/abs/pii/S0022202X22028378
