Pathophysiological functions of self-derived DNA

Abstract

Inflammation plays indispensable roles in building the immune responses such as acquired immunity against harmful pathogens. Furthermore, it is essential for maintaining biological homeostasis in ever-changing conditions. Pattern-recognition receptors (PRRs) reside in cell membranes, endosomes or cytoplasm, and function as triggers for inflammatory responses. Binding of pathogen- or self-derived components, such as DNA, to PRRs activates downstream signaling cascades, resulting in the production of a series of pro-inflammatory cytokines and type I interferons (IFNs). While these series of responses are essential for host defense, the unexpected release of DNA from the nucleus or mitochondria of host cells can lead to autoimmune and autoinflammatory diseases. In this review, we focus on DNA-sensing mechanisms via PRRs and the disorders and extraordinary conditions caused by self-derived DNA.

Graphical Abstract

Keywords:

• PRR
• DNA
• DNA-sensing
• autoimmune disease
• autoinflammatory disease

Acknowledgments

We thank Chihiro Suzuki for secretarial assistance. We would like to thank Guang Han Ong and Editage (www.editage.com) for English language editing.

Disclosure statement

The authors declare no conflict of interest. D.O. and T.K. conceptualized the framework of this review article, wrote, corrected, read and finalized the article. D.O. constructed the figures. All authors approved the submitted version of manuscript.

Additional information

Funding

This work was supported by Japan Science and Technology Agency (JSPS) KAKENHI Grants-in-Aid for Scientific Research (B) 20H03468 (T. K), and JSPS KAKENHI Grant-in-Aid for Early-Career Scientists 21K14817 (D.O.). This work was also supported by the Takeda Science Foundation and JST CREST.