Autophagy, inflammation and innate immunity in inflammatory myopathies

Cristina Cappelletti, Barbara Galbardi, Dimos Kapetis, Gaetano Vattemi, Valeria Guglielmi, Paola Tonin, Franco Salemo, Lucia Morandi, Giuliano Tomelleri, Renato Mantegazza, Pia Bemasconi

Research output: Contribution to journalArticle

Abstract

Autophagy has a large range of physiological functions and its dysregulation contributes to several human disorders, including autoinflammatory/autoimmune diseases such as inflammatory myopathies (IIMs). In order to better understand the pathogenetic mechanisms of these muscular disorders, we sought to define the role of autophagic processes and their relation with the innate immune system in the three main subtypes of IIM, specifically sporadic inclusion body myositis (sIBM), polymyositis (PM), dermatomyositis (DM) and juvenile dermatomyositis (JDM). We found that although the mRNA transcript levels of the autophagy-related genes BECN1, ATG5 and FBX032 were similar in IIM and controls, autophagy activation in all IIM subgroups was suggested by immunoblotting results and confirmed by immunofluorescence. TLR4 and TLR3, two potent inducers of autophagy, were highly increased in IIM, with TLR4 transcripts significantly more expressed in PM and DM than in JDM, sIBM and controls, and TLR3 transcripts highly up-regulated in all IIM subgroups compared to controls. Co-localization between autophagic marker, LC3, and TLR4 and TLR3 was observed not only in sIBM but also in PM, DM and JDM muscle tissues. Furthermore, a highly association with the autophagic processes was observed in all MM subgroups also for some TLR4 ligands, endogenous and bacterial HSP60, other than the high-mobility group box 1 (HMGB1). These findings indicate that autophagic processes are active not only in sIBM but also in PM, DM and JDM, probably in response to an exogenous or endogenous 'danger signal'. However, autophagic activation and regulation, and also interaction with the innate immune system, differ in each type of IIM. Better understanding of these differences may lead to new therapies for the different IIM types.

Original languageEnglish
Article numbere111490
JournalPLoS One
Volume9
Issue number11
DOIs
Publication statusPublished - Nov 3 2014

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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    Cappelletti, C., Galbardi, B., Kapetis, D., Vattemi, G., Guglielmi, V., Tonin, P., Salemo, F., Morandi, L., Tomelleri, G., Mantegazza, R., & Bemasconi, P. (2014). Autophagy, inflammation and innate immunity in inflammatory myopathies. PLoS One, 9(11), [e111490]. https://doi.org/10.1371/joumal.pone.0111490