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T cells play an important role in the development of focal segmental glomerulosclerosis (FSGS). The mechanism underlying such T cell‐based kidney disease, however, remains elusive. Here the authors report that activated CD8 T cells elicit renal inflammation and tissue injury via releasing miR‐186‐5p‐enriched exosomes. Continuing the cohort study identifying the correlation of plasma level of miR‐186‐5p with proteinuria in FSGS patients, it is demonstrated that circulating miR‐186‐5p is mainly derived from activated CD8 T cell exosomes. Renal miR‐186‐5p, which is markedly increased in FSGS patients and mice with adriamycin‐induced renal injury, is mainly delivered by CD8 T cell exosomes. Depleting miR‐186‐5p strongly attenuates adriamycin‐induced mouse renal injury. Supporting the function of exosomal miR‐186‐5p as a key circulating pathogenic factor, intravenous injection of miR‐186‐5p or miR‐186‐5p‐containing T cell exosomes results in mouse renal inflammation and tissue injury. Tracing the injected T cell exosomes shows their preferential distribution in mouse renal tubules, not glomerulus. Mechanistically, miR‐186‐5p directly activates renal tubular TLR7/8 signal and initiates tubular cell apoptosis. Mutating the TLR7‐binding sequence on miR‐186‐5p or deleting mouse TLR7 largely abolishes renal tubular injuries induced by miR‐186‐5p or adriamycin. These findings reveal a causative role of exosomal miR‐186‐5p in T cell‐mediated renal dysfunction. [ABSTRACT FROM AUTHOR]

Development of the acquired resistance is one major obstacle during chemotherapy for cancer patients. Exosomes mediate intercellular communication and cause environmental changes in tumor progression by transmitting active molecules. In this study, the role of long noncoding RNA H19 within exosomes is elucidated in terms of regulating doxorubicin (DOX) resistance of breast cancer. As a result, increased H19 expression was observed in DOX‐resistant breast cancer cells in comparison with the corresponding parental cells. Suppression of H19 significantly lowered DOX resistance by decreasing cell viability, lowering colony‐forming ability, and inducing apoptosis. Moreover, extracellular H19 could be moved to sensitive cells via being incorporated into exosomes. Treating sensitive cells with exosomes from resistant cells increased the chemoresistance of DOX, while downregulation of H19 in sensitive cells abated this effect. Taken together, H19 could be delivered by exosomes to sensitive cells, leading to the dissemination of DOX resistance. Our finding highlights the potential of exosomal H19 as a molecular target to reduce DOX resistance. [ABSTRACT FROM AUTHOR]

Pancreatic cancer is the fourth most lethal malignancy and is characterized by poor immunogenicity. Pancreatic cancer cells have various strategies to suppress host immune response, evade immune defenses, and facilitate tumor growth and development. As a mode of long‐range intercellular communication, cancer‐derived exosomes contribute to impairment of the immune system. However, the mechanisms that induce changes in the activities of signal transduction pathways in immune cells, which are influenced by tumor‐derived exosomes, are poorly understood. We (1) treated peripheral T lymphocytes with pancreatic cancer‐derived exosomes, tagged CD63 with tdTomato, to trace exosome transfer from pancreatic cancer cells to T lymphocytes; (2) carried out a cytotoxicity assay of exosome‐treated T lymphocytes using the Real Time Cellular Analysis system; (3) performed RNA sequencing and gene set enrichment analysis to explore the pivotal signaling pathway that mediates apoptosis in exosome‐treated T lymphocytes; and (4) demonstrated the role of p38 mitogen‐activated protein kinase (MAPK) and endoplasmic reticulum (ER) stress in exosome‐induced T‐lymphocyte apoptosis. In conclusion, these results indicate that pancreatic cancer cells secrete exosomes, which are taken up by T lymphocytes to activate p38 MAPK, and then induce ER stress‐mediated apoptosis, ultimately causing immunosuppression. [ABSTRACT FROM AUTHOR]