Up-regulation of Toll-like receptors 7 and 9 and its potential implications in the pathogenic mechanisms of LMNA-related myopathies

Nucleus. 2018;9(1):398-409. doi: 10.1080/19491034.2018.1471947.


Laminopathies are a heterogeneous group of diseases, caused by mutations in lamin A/C proteins. The most common laminopathy (LMNA-related myopathies, LMNA-RM) affects skeletal and cardiac muscles; muscle histopathology is variable, ranging from mild unspecific changes to dystrophic features, sometimes with inflammatory evidence. Whether the genetic defect might activate innate immune components, leading to chronic inflammation, myofiber necrosis and fibrosis, is still unknown. By qPCR, a significant up-regulation of Toll-like receptor (TLR) 7 and 9 transcripts was found in LMNA-RM compared to other myopathic and non-myopathic muscles. A marked TLR7/9 staining was observed on LMNA-RM blood vessels and muscle fibers and, when present, on infiltrating cells, mainly macrophages, scattered in the tissue or localized close to degenerated muscle fibers and connective tissue. Our results recognize innate immunity as a player in LMNA-RM pathogenesis. Modulation of TLR7/9 signaling pathways and decrease of macrophage-mediated inflammation might be potential therapeutic strategies in LMNA-RM management.

Abbreviations: DMD, Duchenne muscular dystrophy; EDMD2, Emery-Dreifuss muscular dystrophy type 2; FSHD, facio-scapulo-humeral muscular dystrophy; LGMD1B, limb-girdle muscular dystrophy type 1B; LMNA-CMD, LMNA-related congenital muscular dystrophy; LMNA-RM, LMNA-related myopathies; sIBM, sporadic inclusion body myositis; TLR, Toll-like receptor.

Keywords: Laminopathies; Toll-like receptors; macrophages; muscle damage; skeletal muscle.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Child
  • Child, Preschool
  • Humans
  • Infant
  • Lamin Type A / genetics*
  • Lamin Type A / metabolism
  • Middle Aged
  • Muscular Diseases / genetics*
  • Muscular Diseases / metabolism
  • Muscular Diseases / pathology
  • Toll-Like Receptor 7 / genetics*
  • Toll-Like Receptor 7 / metabolism
  • Toll-Like Receptor 9 / genetics*
  • Toll-Like Receptor 9 / metabolism
  • Up-Regulation*
  • Young Adult


  • LMNA protein, human
  • Lamin Type A
  • TLR7 protein, human
  • TLR9 protein, human
  • Toll-Like Receptor 7
  • Toll-Like Receptor 9

Grants and funding

This work was supported by the Italian Ministry of Health (Annual research funding years 2015-2017).