Understanding how Self-RNA Sensing Shapes Human Immune Responses
A central concept in immunology is the idea that our immune system can selectively respond to non-self ligands, while evading immune responses against self-ligands. Pattern recognition receptors (PRRs) are an essential component of this self vs. non-self recognition system as they are responsible for detecting non-self pathogens and activating appropriate immunological responses. A significant proportion of PRRs are specialized in detecting viral DNA or RNA. Since DNA and RNA are the basic building blocks of life across all species, an intriguing question emerges: Can PRRs detect self-DNA or RNA, and what is the biological significance? This is an especially critical question for RNAs, since endogenous RNAs share the same subcellular compartments with many PRRs. Our research program focuses on understanding how self-RNA sensing shapes human immune responses. We are interested in addressing the following key questions:
- How is self-RNA sensing regulated to prevent autoimmunity?
- Does self-RNA sensing by PRRs play critical homeostatic roles?
- Could enhancement or suppression of self-RNA sensing be used for immunomodulatory therapies?
To address these questions, we will use state-of-the-art human cell culture model systems (e.g. human embryonic stem cells), genome engineering, biochemical assays, and bioinformatic tools. With these studies we hope to gain a better understanding of how our immune system suppresses harmful immune responses to self-ligands, while mounting a rapid immune response to pathogens. Furthermore, our studies may serve as a basis for further translational research and future therapeutics since self-nucleic acid sensing by PRRs can cause various autoimmune disorders and may also be harnessed for cancer immunotherapies.