Type i interferon and Toll-like receptor expression characterizes inflammatory myopathies

C. Cappelletti, F. Baggi, F. Zolezzi, D. Biancolini, O. Beretta, M. Severa, E. M. Coccia, P. Confalonieri, L. Morandi, M. Mora, R. Mantegazza, P. Bernasconi

Research output: Contribution to journalArticle

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Abstract

Objectives: Juvenile dermatomyositis (JDM), adult dermatomyositis, and polymyositis (PM) are idiopathic inflammatory myopathies (IIMs) characterized by muscle infiltration and specific muscle fiber alterations. They are thought to have an autoimmune etiology, but triggering factors, and how immunologic attack induces muscle weakness, remain unknown. Recent evidence suggests a key role for type I interferon (IFN)-mediated innate immunity in dermatomyositis, which we explored in JDM, dermatomyositis, and PM by gene expression profiling, and other methods. Methods: Ten IIM and 5 control muscle biopsies were assessed for expression of approximately 16,000 genes by microarray; 37 additional IIM, 10 dystrophinopathic, and 14 nonmyopathic control muscles were studied for type I IFN-dependent genes, and Toll-like receptor (TLR) expression by immunochemistry and PCR. Results: Type I IFN-dependent transcripts were significantly upregulated in IIM muscles compared to controls; in JDM the most expressed were ISG15 (408-fold), IFIT3 (261-fold), MX1 (99-fold), and IRF7 (37-fold). IFN-β (but not IFN-α) transcripts were upregulated in PM as well as dermatomyositis/JDM. TLR3 was upregulated particularly in JDM, being localized on vascular endothelial cells, muscle infiltrating cells (mainly myeloid dendritic cells), and regenerating myofibers; TLR7 and TLR9 proteins were present in IIM (prominently in PM), mainly on cell infiltrates, particularly plasma cells, and on some injured myofibers. Conclusions: IFN-β and type I IFN-induced molecules are involved in PM as well as JDM/dermatomyositis. Endosomal TLRs (effectors of innate immunity) are also involved (but differently) in the 3 conditions, further suggesting viral involvement, although TLR activation could be secondary to tissue damage.

Original languageEnglish
Pages (from-to)2079-2088
Number of pages10
JournalNeurology
Volume76
Issue number24
DOIs
Publication statusPublished - Jun 14 2011

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Myositis
Dermatomyositis
Toll-Like Receptors
Interferon Type I
Interferons
Muscles
Polymyositis
Innate Immunity
Toll-Like Receptor 9
Immunochemistry
Muscle Weakness
Immunologic Factors
Gene Expression Profiling
Myeloid Cells
Plasma Cells
Dendritic Cells
Muscle Cells
Genes
Juvenile dermatomyositis
Endothelial Cells

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Type i interferon and Toll-like receptor expression characterizes inflammatory myopathies. / Cappelletti, C.; Baggi, F.; Zolezzi, F.; Biancolini, D.; Beretta, O.; Severa, M.; Coccia, E. M.; Confalonieri, P.; Morandi, L.; Mora, M.; Mantegazza, R.; Bernasconi, P.

In: Neurology, Vol. 76, No. 24, 14.06.2011, p. 2079-2088.

Research output: Contribution to journalArticle

Cappelletti C, Baggi F, Zolezzi F, Biancolini D, Beretta O, Severa M et al. Type i interferon and Toll-like receptor expression characterizes inflammatory myopathies. Neurology. 2011 Jun 14;76(24):2079-2088. https://doi.org/10.1212/WNL.0b013e31821f440a
Cappelletti, C. ; Baggi, F. ; Zolezzi, F. ; Biancolini, D. ; Beretta, O. ; Severa, M. ; Coccia, E. M. ; Confalonieri, P. ; Morandi, L. ; Mora, M. ; Mantegazza, R. ; Bernasconi, P. / Type i interferon and Toll-like receptor expression characterizes inflammatory myopathies. In: Neurology. 2011 ; Vol. 76, No. 24. pp. 2079-2088.
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AU - Beretta, O.

AU - Severa, M.

AU - Coccia, E. M.

AU - Confalonieri, P.

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