Despite the conclusion of the COVID-19 pandemic, novel infectious diseases keep appearing, presenting persistent viral dangers that require strong and enduring immune protections. That said, overzealous immune activities can also damage the body’s own tissues, resulting in serious medical complications. Researchers from KAIST, along with an international collaboration, have pinpointed a vital protein functioning as a ‘switch’ to control immune reactions against viruses. This significant finding is poised to establish a foundation for managing future infectious outbreaks and developing treatments for autoimmune disorders.
Breakthrough Discovery on Immune Regulation
On May 14, KAIST (under President Kwang-Hyung Lee) revealed that a collaborative team, spearheaded by Professor Yoosik Kim from the Department of Chemical and Biomolecular Engineering at KAIST and Professor Seunghee Cha from the University of Florida, has elucidated the process through which double-stranded RNA originating from mitochondria intensifies immune reactions. The team pinpointed the protein SLIRP as an essential ‘immune switch’ that governs this mechanism, holding substantial importance in viral infections as well as autoimmune conditions.
Understanding Autoimmune Diseases
Autoimmune disorders occur when the immune system erroneously targets the body’s own components instead of external invaders, launching attacks against healthy tissues. Although there has been considerable investigation, the exact origins of severe inflammatory states such as Sjögren’s syndrome and systemic lupus erythematosus are not fully understood, leaving treatment options quite restricted.
Investigating Mitochondrial Double-Stranded RNA
In their pursuit to reveal the molecular pathways behind immune overactivation and to pinpoint possible control elements, Professor Yoosik Kim’s research group concentrated on mitochondrial double-stranded RNA (mt-dsRNA). This material, generated inside cellular mitochondria, acts as an immunogenic agent. Because mt-dsRNA bears a strong resemblance to viral RNA in structure, it has the potential to inadvertently provoke immune alerts even without any real viral presence.
The scientists found that SLIRP serves as a primary controller of mt-dsRNA, enhancing immune signals by maintaining the stability of this RNA. Through experiments mimicking the tissues of autoimmune disease sufferers and viral infection scenarios, they observed heightened SLIRP expression. On the flip side, when SLIRP was inhibited, the immune activation dropped markedly, confirming its pivotal position in boosting immune activity.
Dual Role of SLIRP in Health Contexts
Further analysis in this research illustrated SLIRP’s versatile roles depending on the situation. In cell cultures exposed to human beta coronavirus OC43 and encephalomyocarditis virus (EMCV), blocking SLIRP diminished the antiviral defenses, allowing greater viral proliferation. In contrast, within blood samples and salivary gland cells from individuals with Sjögren’s syndrome—where levels of both SLIRP and mt-dsRNA were notably high—inhibiting SLIRP effectively toned down the erratic immune overreactions.
Such results position SLIRP as a central molecular toggle that modulates immune behaviors across infectious diseases and autoimmune pathologies alike.
Implications for Future Therapies
Professor Yoosik Kim commented, “Our research has unveiled SLIRP as a key protein responsible for amplifying immune responses through mt-dsRNAs. With its involvement in both autoimmune conditions and viral threats, SLIRP emerges as an attractive candidate for targeted therapies aimed at balancing immune functions in a range of inflammatory scenarios.”
The publication featured major contributions from Ph.D. candidate Do-Young Ku (lead author) and M.S. student Ye-Won Yang (co-author), both from KAIST’s Department of Chemical and Biomolecular Engineering. It appeared online in the prestigious journal Cell Reports on April 19, 2025.
Funding for this work came from the Ministry of Health and Welfare’s Public Health Technology Research Program, as well as support from the National Institutes of Health (NIH) via a Research Project (R01) grant.
