Recently, researchers Liu Xu, Huang Wei, Zhang Xiwen, and colleagues from the Jiangsu Provincial Key Laboratory of Critical Care Medicine at Southeast University published an original study in the Journal of Extracellular Vesicles, the official journal of the International Society for Extracellular Vesicles (ISEV). The paper, titled “Endothelium-Treg Communication Through Extracellular Vesicle Transfer Exacerbates Acute Respiratory Distress Syndrome,” reveals a new mechanism underlying the uncontrolled inflammatory response in acute lung injury (ALI) and acute respiratory distress syndrome (ARDS): the EV-mediated pulmonary endothelial-Treg communication axis is a critical link in the immune imbalance characteristic of ALI/ARDS.

ALI and ARDS are common critical illnesses in clinical settings, characterized by rapid onset, rapid progression, and high mortality rates. The early uncontrolled pulmonary inflammatory response is the fundamental cause of ALI/ARDS development. A reduction in the number and proportion of regulatory T cells (Tregs) within the lungs is a key factor in this uncontrolled inflammation. It is closely associated with poor patient prognosis, though the underlying mechanism remains unclear.

This study identified extracellular vesicles derived from pulmonary vascular endothelial cells (EC-EVs) as important regulators of the inflammatory response in the lungs. These EC-EVs can influence the differentiation of na?ve CD4+ T cells into Tregs, thereby weakening the anti-inflammatory response in the lungs and exacerbating lung injury. Bioinformatics analysis, together with subsequent mechanistic studies, revealed that during ALI/ARDS, EC-EVs contain high levels of the transcription factor mediator 1 (MED1). MED1 inhibits Treg differentiation by activating the IL-21/STAT3 signaling pathway. This research provides a novel explanation for the early reduction of pulmonary Tregs in ALI/ARDS and offers a potential target and new strategy for early intervention and treatment in ARDS.

The co-first authors of this paper include doctoral student Liu Xu, Associate Researcher Huang Wei, and Associate Chief Physician Zhang Xiwen from the School of Medicine, SEU. The corresponding authors include Prof. Xie Jianfeng, Prof. Zheng Mingzhu, Prof. Chao Jie, and Prof. Qiu Haibo. This work has been supported by the Key Program of the National Natural Science Foundation of China.

Source: Jiangsu Provincial Key Laboratory of Critical Care Medicine

Translated by: Melody Zhang

Proofread by: Gao Min

Edited by: Leah Li