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In Vitro Differentiation Model of Human Normal Memory B Cells to Long-lived Plasma Cells
Published on: January 20, 2019
Extracellular vesicle-derived mir-148a-3p promotes plasmablast differentiation in bullous pemphigoid via BACH2
Jine Zhang1, Jieyu Zhang1, Shengxian Shen1
1Department of Dermatology, Xijing Hospital, Fourth Military Medical University; Xi'an, Shaanxi, China.
Abstract:
Bullous pemphigoid (BP) is an autoimmune blistering disease characterized by the production of autoantibodies; however, the molecular mechanisms regulating plasma cell differentiation remain unclear. This study investigated the role of plasma-derived extracellular vesicles (EVs) and their microRNA cargo in regulating this process. EVs isolated from patients with BP and healthy controls were functionally assessed. BP-derived EVs significantly enhanced plasmablast differentiation, increased pathogenic autoantibody production, and elevated IL-6 secretion. High-throughput sequencing identified miR-148a-3p as a selectively enriched and functionally critical microRNA within BP EVs. Mechanistically, miR-148a-3p promoted plasmablast differentiation by targeting the BACH2/mTOR signaling pathway. This was validated using dual-luciferase reporter assays, western blotting, RT-qPCR, and flow cytometry. These findings reveal, to our knowledge, a previously unrecognized EV-mediated regulatory mechanism in BP pathogenesis and identify miR-148a-3p as a potential diagnostic biomarker and therapeutic target.
