RETRACTED: Mechanisms of M2 Macrophage-Derived Exosomal Long Non-coding RNA PVT1 in Regulating Th17 Cell Response in Experimental Autoimmune Encephalomyelitisa

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.

Mesenchymal stem cell-derived exosomes regulate the polarization and inflammatory response of macrophages via miR-21-5p to promote repair after myocardial reperfusion injury

“…miRNA is a crucial component of EXOs and determines the effect of EXOs on receptor cells. Some miRNAs found in MSC-EXOs play key roles in immune regulation, such as miR-125a (21), miR-146a (16), miR-181b (22), miR-223 (23), and miR-21-5p (24). In previous experiments, we found that the expression level of miR-21-5p in MSC-EXOs was higher than that in macrophage-derived exosomes.…”

The Biogenesis, Biological Functions, and Applications of Macrophage-Derived Exosomes

“…Long non-coding RNAs (lncRNAs) play key roles in multiple diseases. Wu et al reported that the lncRNA PVT1 carried by M2-Exos acts as a miR-21-5p sponge to upregulate the cytokine signaling repressor protein, SOCS5 and inactivates the JAKs/STAT3 pathway ( Wu et al, 2020b ). M1-Exos containing miR-16-5p inhibit gastric cancer progression by activating T-cell immune responses through PD-L1 ( Li et al, 2020b ).…”

Competing Endogenous RNA Networks as Biomarkers in Neurodegenerative Diseases

“…This, together with its power to recruit immune cells, would aggravate the disease [ 87 ]. On the other hand, lncRNA PVT1 is downregulated in MS patients [ 232 ] and in the spinal cord of EAE mice [ 88 ]. Wu et al demonstrated that it acts as a ceRNA for miR-21-5p, thus regulating the expression of SOCS5 [ 88 ], a protein from the suppressor of cytokine signaling (SOCS) family, which is also downregulated in MS patients [ 233 ].…”

“…On the other hand, lncRNA PVT1 is downregulated in MS patients [ 232 ] and in the spinal cord of EAE mice [ 88 ]. Wu et al demonstrated that it acts as a ceRNA for miR-21-5p, thus regulating the expression of SOCS5 [ 88 ], a protein from the suppressor of cytokine signaling (SOCS) family, which is also downregulated in MS patients [ 233 ]. SOCSs proteins are rapidly transcribed in response to intracellular JAK-STAT signaling [ 234 ], regulating the cytokine-induced immune response and therefore playing an important for the progression of multiple sclerosis [ 233 ].…”