miR-132 suppresses autoimmune encephalomyelitis by inducing cholinergic anti-inflammation: a novel Ahr-based exploration
-
1
King Faisal University, Biological Sciences Department, Saudi Arabia
microRNAs (miRNAs) are small group of RNAs that are emerging as new avenue by which the autoimmune diseases are modulated. Increasing paradigm shows that miRNAs are involved in pathogenesis of multiple sclerosis (MS). However, the interaction of miRNAs with environmental-responsive transcription factors that play prominent roles in MS is unexplored. Therefore, identification of a new mechanism that links these two player in MS development could enable earlier treatment. Activation of aryl hydrocarbon receptor (Ahr) by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) alleviates inflammation in Experimental Autoimmune Encephalomyelitis (EAE), the best MS model; therefore, we predicted that TCDD ameliorates EAE by inducing miRNA(s) targeting inflammatory mediators. Here, we provide evidences about new miRNA-based mechanism through which activation of Ahr by TCDD induced cholinergic anti-inflammation in EAE mice by upregulating the expression of acetylcholiesterase (AChE)-targeting miR-132. CD4+CD62L+ cells purified from spleens of wild type or Ahr-/- C57BL/6 mice were stimulated with TGF-β alone or combined with IL-6 in presence of TCDD. EAE was induced by MOG35-55 with/without i.p. injection with TCDD. Gene expression was measured by qPCR. AChE protein was quantified by immunoblotting, and cytokines were measured by ELISA. We found that activation of Ahr by TCDD induced miR-132, and its cluster partner miR-212, in T cells in vitro and in vivo. Treating EAE mice with TCDD alleviated EAE symptoms, manifested by reciprocal relation between miR-132 and AChE and pro-inflammatory cytokines. In conclusion, TCDD-activated Ahr mitigates autoimmune inflammation by miR-132-mediated cholinergic anti-inflammation. Therefore, our findings may form a base for future application of miR-132 mimics in treatment of MS.
Keywords:
EAE/MS,
AhR,
microRNA,
miR-132,
Cholinergic anti-inflammation
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Immune-mediated disease pathogenesis
Citation:
Hanieh
HN and
Alzahrani
AM
(2013). miR-132 suppresses autoimmune encephalomyelitis by inducing cholinergic anti-inflammation: a novel Ahr-based exploration.
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.00043
Copyright:
The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers.
They are made available through the Frontiers publishing platform as a service to conference organizers and presenters.
The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated.
Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed.
For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions.
Received:
08 Mar 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Dr. Hamza N Hanieh, King Faisal University, Biological Sciences Department, Alhasa, Saudi Arabia, hhanieh@ahu.edu.jo