Objective: The triggering factor of inflammation in idiopathic inflammatory myopathies (IIMs) is still unknown and an involvement of viruses or bacteria has been put forward. We sought to investigate the expression of type I interferons (IFNα/β) and of endosomal Toll-like receptors (TLRs) in IIM muscles. Methods: Ten IIM and 5 control muscle biopsies were assessed by microarray analysis for the expression of approximately 16,000 genes; 37 additional samples from IIM and controls were studied for IFNα/β-dependent genes and intracellular TLR expression using immunohistochemistry, confocal miscroscopy, real-time quantitative and qualitative PCR. Results: IFNα/β-dependent gene transcripts were up-regulated in all IIM muscle specimens compared to controls. In juvenile dermatomyositis (JDM) ISG15 (408-fold), IFIT3 (261-fold), MX1 (99-fold), IRF7 (37-fold) were those most expressed. TLR3, TLR7 and TLR9 were differentially expressed in IIM muscles: TLR3 was highly up-regulated in JDM, localized on vascular endothelial cells, muscle infiltrating cells and regenerating myofibers; TLR7 and TLR9 were frequently detected in polymyositis (PM), mainly on cell infiltrates (particularly plasma cells), and on some injured myofibers. Conclusion: Transcriptome analysis indicated that IFNα/β-induced molecules play a key role in the pathogenesis of IIMs, particularly in JDM. Endosomal TLRs represent important effector molecules that link innate and adaptive immune responses in affected muscles, showing their potential as new therapeutic targets for the IIM treatment.

(2009). Type I interferons and toll-like receptors are linked to pathological alterations of idiopathic inflammatory myopathiens. (Tesi di dottorato, Università degli Studi di Milano-Bicocca, 2009).

Type I interferons and toll-like receptors are linked to pathological alterations of idiopathic inflammatory myopathiens

CAPPELLETTI, CRISTINA
2009-11-27

Abstract

Objective: The triggering factor of inflammation in idiopathic inflammatory myopathies (IIMs) is still unknown and an involvement of viruses or bacteria has been put forward. We sought to investigate the expression of type I interferons (IFNα/β) and of endosomal Toll-like receptors (TLRs) in IIM muscles. Methods: Ten IIM and 5 control muscle biopsies were assessed by microarray analysis for the expression of approximately 16,000 genes; 37 additional samples from IIM and controls were studied for IFNα/β-dependent genes and intracellular TLR expression using immunohistochemistry, confocal miscroscopy, real-time quantitative and qualitative PCR. Results: IFNα/β-dependent gene transcripts were up-regulated in all IIM muscle specimens compared to controls. In juvenile dermatomyositis (JDM) ISG15 (408-fold), IFIT3 (261-fold), MX1 (99-fold), IRF7 (37-fold) were those most expressed. TLR3, TLR7 and TLR9 were differentially expressed in IIM muscles: TLR3 was highly up-regulated in JDM, localized on vascular endothelial cells, muscle infiltrating cells and regenerating myofibers; TLR7 and TLR9 were frequently detected in polymyositis (PM), mainly on cell infiltrates (particularly plasma cells), and on some injured myofibers. Conclusion: Transcriptome analysis indicated that IFNα/β-induced molecules play a key role in the pathogenesis of IIMs, particularly in JDM. Endosomal TLRs represent important effector molecules that link innate and adaptive immune responses in affected muscles, showing their potential as new therapeutic targets for the IIM treatment.
MANTEGAZZA, RENATO
endosomal TLRs, idiopathic inflammatory myopathies, type I interferons
MED/04 - PATOLOGIA GENERALE
English
Scuola di Dottorato in Medicina Traslazionale e Molecolare
MEDICINA TRASLAZIONALE E MOLECOLARE (DIMET) - 45R
22
2008/2009
(2009). Type I interferons and toll-like receptors are linked to pathological alterations of idiopathic inflammatory myopathiens. (Tesi di dottorato, Università degli Studi di Milano-Bicocca, 2009).
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10281/9235
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