Detecting microbial nucleic acids through pattern recognition receptors (PRRs) is crucial for triggering anti-microbial immune responses. However, PRRs that specialize in nucleic acid sensing often struggle to distinguish between microbial and endogenous (self)-nucleic acids, leading to potential autoimmune and inflammatory diseases when self-nucleic acids are mistakenly recognized. To prevent these harmful immune responses, multiple safeguard mechanisms have evolved.
One such mechanism involves the endonuclease deoxyribonuclease 1-like 3 (DNASE1L3). Produced by innate immune cells like dendritic cells and macrophages, DNASE1L3 degrades self-DNA from dying cells, preventing it from activating nucleic acid sensing PRRs and protecting the host from systemic autoimmune syndromes. Recently, endogenous DNA has also been implicated in the chronic low-grade inflammation associated with obesity, contributing to complications such as type II diabetes. In this seminar, we will explore the physiological functions of DNASE1L3 and present our latest findings on its role in regulating obesity-related inflammation.

Vanja Sisirak is invited by Julie Helft.