tRNA-derived fragments in T lymphocyte–beta cell crosstalk and in type 1 diabetes pathogenesis in NOD mice – published online 05/07/2024

Flora Brozzi, Cécile Jacovetti, Cristina Cosentino, Véronique Menoud, Kejing Wu, Mustafa Bilal Bayazit, Baroj Abdulkarim, Christian Iseli, Nicolas Guex, Claudiane Guay, Romano Regazzi

Immune cells that invade the islets of Langerhans during the initial phases of type 1 diabetes release proinflammatory mediators that cause beta cell dysfunction and death. In this issue, Brozzi et al (https://doi.org/10.1007/s00125-024-06207-3) report that beta cell failure in NOD mice is associated with changes in the levels of many small non-coding RNAs generated by tRNA fragmentation. The authors show that, although some of these changes are triggered by chronic exposure of beta cells to proinflammatory cytokines, others result from the direct transfer via extracellular vesicles of tRNA-derived fragments from the invading lymphocytes to insulin-secreting cells. Some of the tRNA fragments transferred to beta cells during the early phases of type 1 diabetes promote apoptosis of insulin-secreting cells. The authors conclude that that the delivery of this novel class of small non-coding RNAs produced by lymphocytes via extracellular vesicles may contribute to the autoimmune attack against insulin-secreting beta cells and the development of type 1 diabetes.