Publications

Latest publication 12/31/2012

Implication of double-stranded RNA signaling in the etiology of autoimmune myast

Objective: Myasthenia gravis (MG) is an autoimmune disease mediated mainly by anti–acetylcholine receptor (AChR) antibodies. The thymus plays a...

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    [title] => Implication of double-stranded RNA signaling in the etiology of autoimmune myast
    [paragraph] => Implication of double-stranded RNA signaling in the etiology of autoimmune myasthenia gravis
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Authors
P. Cufi, N. Dragin, J. M. Weiss, P. Martinez-Martinez, M. H. De Baets, R. Roussin et al.

 Lab
CNRS, Paris, France.
Journal
Annals of Neurology
Abstract
Objective:
Myasthenia gravis (MG) is an autoimmune disease mediated mainly by anti–acetylcholine receptor (AChR) antibodies. The thymus plays a primary role in MG pathogenesis. As we recently showed an inflammatory and antiviral signature in MG thymuses, we investigated whether pathogen-sensing molecules could contribute to an anti-AChR response.
Methods:
We studied the effects of toll-like receptor agonists on the expression of α-AChR and various tissue-specific antigens (TSAs) in human thymic epithelial cell (TEC) cultures. As polyinosinic–polycytidylic acid (poly[I:C]), which mimics double-stranded RNA (dsRNA), stimulated specifically α-AChR expression, the signaling pathways involved were investigated. In parallel, we analyzed the expression of dsRNA-signaling components in the thymus of MG patients, and the relevance of our data was investigated in vivo in poly(I:C)-injected mice.
Results:
We demonstrate that dsRNA signaling induced by poly(I:C) specifically triggers the overexpression of α-AChR in TECs and not of other TSAs. A poly(I:C) effect was also observed on MG TECs. This induction is mediated through toll-like receptor 3 (TLR3) and protein kinase R (PKR), and by the release of interferon (IFN)-β. In parallel, human MG thymuses also display an overexpression of TLR3, PKR, and IFN-β. In addition, poly(I:C) injections specifically increase thymic expression of α-AChR in wild-type mice, but not in IFN-I receptor knockout mice. These injections also lead to an anti-AChR autoimmune response characterized by a significant production of serum anti-AChR antibodies and a specific proliferation of B cells.
Interpretation:
Because anti-AChR antibodies are highly specific for MG and are pathogenic, dsRNA-signaling activation could contribute to the etiology of MG.
BIOSEB Instruments Used
Grip strength test (BIO-GS3)

Keywords/Topics
General muscular system; Muscular system
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An easy way to objectively quantify the muscular strength of mice and rats, and to assess the effect of drugs, toxins, muscular (i.e. myopathy) and neurodegenerative diseases on muscular degeneration. It is widely used in conjunction with the ROTAROD motor coordination test: a normally coordinated rodent will show a decreased latency to fall off the rotating rod if its muscular strength is low. The Grip Strength Test is a must for your research on activity, motor control & coordination, and is particularly well suited for studies on Parkinson's & Huntington's disease.
New features GS4 - 2023: Color display with permanent backlight screen for easier reading, reset by footswitch, Improved battery time, Larger data memory of 500 values, Animal counter, USB port (charging/data transfer)

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