Mesenchymal stromal cells alleviate acute respiratory distress syndrome through the cholinergic anti-inflammatory pathway

作     者：Xiaoran Zhang Xuxia Wei Yiwen Deng Xiaofeng Yuan Jiahao Shi Weijun Huang Jing Huang Xiaoyong Chen Shuwei Zheng Jieying Chen Keyu Chen Ruiming Xu Hongmiao Wang Weiqiang Li Shiyue Li Huimin Yi Andy Peng Xiang 

作者机构：Department of Surgical Intensive CareThe Third Affiliated HospitalSun Yat-Sen UniversityGuangzhouGuangdong 510630China Center for Stem Cell Biology and Tissue EngineeringKey Laboratory for Stem Cells and Tissue EngineeringMinistry of EducationSun Yat-Sen UniversityGuangzhouGuangdong 510080China National-Local Joint Engineering Research Center for Stem Cells and Regenerative MedicineZhongshan School of MedicineSun Yat-Sen UniversityGuangzhouGuangdong 510080China Department of General Intensive Care UnitLingnan HospitalThe Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong 510530China Department of AnesthesiologyThe First Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdong 510080China State Key Laboratory of Respiratory Disease and National Clinical Research Center for Respiratory Diseasethe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou Medical UniversityGuangzhouGuangdong 510120China 

出 版 物：《Signal Transduction and Targeted Therapy》 (信号转导与靶向治疗（英文）)

年 卷 期：2022年第7卷第10期

页      面：3884-3897页

核心收录：

学科分类：0710[理学-生物学] 1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

基　　金：supported by the National Key Research and Development Program of China,Stem Cell and Translational Research(2018YFA0107200,2019YFA0110303,2021YFA1100600) National Natural Science Foundation of China(81730005,32130046,81900075,81970109,82170540,81721003) Natural Science Foundation of Guangdong Province(2018A0303130305,2021A1515011759,2022A1515012452,2022A1515011919) Key Research and Development Program of Guangdong Province(2019B020236002) Key Scientific and Technological Program of Guangzhou City(201803040011),and Pearl River S&T Nova Program of Guangzhou(201906010095) 

主　　题：distress cholinergic inflammation 

摘      要：Mesenchymal stromal cells(MSCs)have been considered a promising alternative for treatment of acute respiratory distress syndrome(ARDS).However,there is significant heterogeneity in their therapeutic efficacy,largely owing to the incomplete understanding of the mechanisms underlying the therapeutic activities of ***,we hypothesize that the cholinergic antiinflammatory pathway(CAP),which is recognized as a neuroimmunological pathway,may be involved in the therapeutic mechanisms by which MSCs mitigate *** lipopolysaccharide(LPS)and bacterial lung inflammation models,we found that inflammatory cell infiltration and Evans blue leakage were reduced and that the expression levels of choline acetyltransferase(ChAT)and vesicular acetylcholine transporter(VAChT)in lung tissue were significantly increased 6 hours after MSC *** the vagus nerve was blocked orα7 nicotinic acetylcholine(ACh)receptor(α7nAChR)-knockout mice were used,the therapeutic effects of MSCs were significantly reduced,suggesting that the CAP may play an important role in the effects of MSCs in ARDS *** results further showed that MSC-derived prostaglandin E2(PGE2)likely promoted ACh synthesis and ***,based on the efficacy of nAChR andα7nAChR agonists,we found that lobeline,the nicotinic cholinergic receptor excitation stimulant,may attenuate pulmonary inflammation and alleviate respiratory symptoms of ARDS patients in a clinical study(ChiCTR2100047403).In summary,we reveal a previously unrecognized MSC-mediated mechanism of CAP activation as the means by which MSCs alleviate ARDS-like syndrome,providing insight into the clinical translation of MSCs or CAP-related strategies for the treatment of patients with ARDS.