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ID 116996
Title Alternative
DNA Sensors in Vascular and Metabolic Diseases
Author
Pham, Phuong Tran Tokushima University
Keywords
DNA sensor
TLR9
STING
Atherosclerosis
Insulin resistance
Inflammation
Content Type
Journal Article
Description
Sterile chronic inflammation causes cardiometabolic disorders; however, the mechanisms are not fully understood. Previous studies have demonstrated the degradation of cells/tissues in the vasculature and metabolic organs in lifestyle-associated diseases, such as diabetes and hyperlipidemia, suggesting the release and/or accumulation of nucleic acids from damaged cells. DNA is indispensable for life; however, DNA fragments, especially those from pathogens, strongly induce inflammation by the activation of DNA sensors. Growing evidence suggests that DNA-sensing mechanisms, which are normally involved in self-defense against pathogens as the innate immune system, are associated with the progression of inflammatory diseases in response to endogenous DNA fragments. There are several types of DNA sensors in our bodies. Toll-like receptor 9 (TLR9)—one of the most studied DNA sensors—recognizes DNA fragments in endosome. In addition, stimulator of interferon genes (STING), which has recently been extensively investigated, recognizes cyclic GMP-AMP (cGAMP) generated from DNA fragments in the cytosol. Both TLR9 and STING are known to play pivotal roles in host defense as the innate immune system. However, recent studies have indicated that the activation of these DNA sensors in immune cells, such as macrophages, promotes inflammation leading to the development of vascular and metabolic diseases associated with lifestyle. In this review, we discuss recent advances in determining the roles of DNA sensors in these disease contexts. Revealing a novel mechanism of sterile chronic inflammation regulated by DNA sensors might facilitate clinical interventions for these health conditions.
Journal Title
Journal of Atherosclerosis and Thrombosis
ISSN
18803873
13403478
Publisher
Japan Atherosclerosis Society
Volume
29
Issue
3
Start Page
297
End Page
307
Published Date
2022-03-01
Rights
This article is distributed under the terms of the latest version of CC BY-NC-SA defined by the Creative Commons Attribution License (https://creativecommons.org/licenses/by-nc-sa/4.0/).
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DOI (Published Version)
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language
eng
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departments
Medical Sciences