MicroRNA-132 suppresses autoimmune encephalomyelitis by inducing cholinergic anti-inflammation: a new Ahr-based exploration.

Abstract

MicroRNAs (miRNAs) are a small group of RNAs that are emerging as a new avenue by which autoimmune diseases may be modulated. Accumulating evidence shows that miRNAs are involved in the pathogenesis of MS; however, the interaction of miRNAs with environmentally responsive transcription factors that play prominent roles in MS is unexplored. The activation of aryl hydrocarbon receptor by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) alleviates inflammation in experimental autoimmune encephalomyelitis (EAE), the best available model of MS. Therefore, we predicted that TCDD could attenuate EAE by inducing miRNA(s) targeting inflammatory mediators. Here, we show that TCDD induces cholinergic anti-inflammation in EAE mice by upregulating acetylcholinesterase-targeting miR-132. The expression of miR-132 was downregulated in CD4⁺ cells and associated with EAE severity, while TCDD treatment attenuated EAE by inducing the miR-132/acetylcholinesterase module. Silencing miR-132 in vivo abolished TCDD-induced cholinergic anti-inflammation and aggravated EAE. Overexpression of miR-132 in encephalitogenic CD4⁺ cells decreased IL-17 and IFN-γ and suppressed T-cell proliferation. In conclusion, our findings identify a new miRNA-based mechanism through which miR-132 mediates TCDD-induced EAE attenuation, suggesting that miR-132 could be a promising therapeutic target for anti-inflammatory treatment of MS.

• Authors: Hamza Hanieh, Abdullah Alzahrani
• Journal: European journal of immunology (Eur J Immunol) Vol. 43 Issue 10 Pg. 2771-82 (Oct 2013) ISSN: 1521-4141 [Electronic] Germany
• PMID: 23780851 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical References

• Interleukin-17
• MIRN132 microRNA, mouse
• MicroRNAs
• Polychlorinated Dibenzodioxins
• Receptors, Aryl Hydrocarbon
• Interferon-gamma
• Acetylcholinesterase

Topics

• Acetylcholinesterase (genetics, metabolism)
• Animals
• CD4-Positive T-Lymphocytes (immunology)
• Cell Proliferation
• Cells, Cultured
• Encephalomyelitis, Autoimmune, Experimental (immunology, therapy)
• Gene Expression Regulation
• Humans
• Interferon-gamma (genetics, metabolism)
• Interleukin-17 (genetics, metabolism)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• MicroRNAs (genetics, immunology, metabolism)
• Molecular Targeted Therapy
• Multiple Sclerosis (immunology, therapy)
• Polychlorinated Dibenzodioxins (administration & dosage, adverse effects)
• Receptors, Aryl Hydrocarbon (genetics, metabolism)
• Transgenes (genetics)