Elevated tRNA Halves in Olfactory Epithelial Cells of Patients with Schizophrenia

Dr. Yohei Kirino, Professor and Vice Chair for Research in the Department of Biochemistry and Molecular Biology, and his team have recently identified a novel molecular mechanism that contributes to the neuroinflammation and immune dysregulation observed in schizophrenia. The study, which was published recently in the Journal of Clinical Investigation, reveals that individuals with the disorder exhibit significantly elevated levels of immunostimulatory tRNA half molecules within olfactory epithelial cells. By analyzing these neural-derived cells as a reachable proxy for neural tissue, the researchers discovered that specific tRNA halves—known to trigger the TLR7 immune pathway—are upregulated in tandem with Angiogenin, the enzyme responsible for their production. This link between elevated tRNA halves and the induction of pro-inflammatory cytokines offers a potential molecular explanation for chronic inflammation in the central nervous system, highlighting a novel mechanism underlying schizophrenia pathophysiology. Ultimately, this discovery opens new avenues for developing diagnostic biomarkers and targeted therapies aimed at mitigating the immune-driven aspects of neuropsychiatric conditions, potentially leading to more effective management strategies for a disorder that currently has limited treatment options.  These studies represent a collaboration between Dr. Kirino’s team and the research groups led by Dr. Chang-Gyu Hahn and Dr. Karin Borgmann-Winter in the Department of Psychiatry at SKMC.