Mechanisms of M2 Macrophage-Derived Exosomal Long Non-coding RNA PVT1 in Regulating Th17 Cell Response in Experimental Autoimmune Encephalomyelitisa
Authors: Lei Wu
Wei Fang
Peng Huang
Jinjin Xia
Donghui Li
Ying Kang
Journal: Frontiers in Immunology (2020)
Discipline: IMMUNOLOGY
Keywords: M2 macrophages; SOCS5; exosomes; experimental autoimmune encephalomyelitis; long non-coding RNA PVT1
Affiliations: Department of Neurology, The Second Affiliated Hospital of Zhejiang, University School of Medicine, Hangzhou, China., Department of Neurology, Changxing Hospital, Second Affiliated Hospital of Medical College of Zhejiang University, Huzhou, China., Department of Pollution Source Statistics, Zhejiang Provincial Environmental Monitoring Center, Hangzhou, China., School of Pharmacy, Anhui University of Traditional Chinese Medicine, Hefei, China.

Abstract:  Long non-coding RNA (lncRNA) is pivotal for multiple sclerosis (MS), but the potential mechanism of lncRNA PVT1 in MS animal model, experimental autoimmune encephalomyelitis (EAE) still remains unclear. In this study, macrophages were firstly isolated and induced to polarize into M2 macrophages. M2 macrophage-derived exosomes (M2-exos) were extracted and identified, and EAE mouse model was established and treated with M2-exos. The effect of M2-exos on EAE mice was evaluated by clinical scores. The proportion of Treg and Th17 cells in spinal cord cells and splenocytes, and levels of inflammatory factors were measured. The targeting relationships among PVT1, miR-21-5p, and SOCS5 were verified. The expression of JAKs/STAT3 pathway-related proteins was measured. After M2-exo treatment, the clinical score of EAE mice decreased, and demyelination and inflammatory infiltration improved; Th17 cells decreased, Treg cells increased, and the levels of inflammatory factors decreased significantly. SOCS5 and PVT1 were downregulated and miR-21-5p was upregulated in EAE mice. PVT1 could sponge miR-21-5p to regulate SOCS5. SOCS5 alleviated EAE symptoms by repressing the JAKs/STAT3 pathway. Together, M2-exos-carried lncRNA PVT1 sponged miR-21-5p to upregulate SOCS5 and inactivate the JAKs/STAT3 pathway, thus reducing inflammation and protecting EAE mice. This study may offer novel treatments for MS. 

Retracted: Yes

PubPeer comments:
 First, the way many FACS plots are presented is strange, as you can see in the figure below: Scaling for fluorescence channels is usually log, here many CD4 stainings in Fig.4 are linear scale, which would correspond to the very far right of the x axis ![file] , 
 Second, one can find identical dot pattern in the FACS dot plots of Fig4.B and Fig.6C. Additionally, some dot pattern are found in both 4B and 6C Figure 4B ![file] Figure 6C ![file] Pattern found in both: ![file] , 
 #1 So vertical scales are linear (in units of  K ). Horizontal scales are labeled as logarithmic but have linear-spaced tick-marks. What plotting software will produce results like that? , 
 **RETRACTED** https: www.frontiersin.org articles 10.3389 fimmu.2021.773900 full The journal retracts the 04 September 2020 article cited above. u201cFollowing publication, concerns were raised regarding the integrity of the data in the published figures. The authors failed to provide a satisfactory explanation during the investigation, which was conducted in accordance with Frontiersu2019 policies. ,