The kinesin superfamily motor protein KIF4 is associated with immune cell activation in idiopathic inflammatory myopathies

Pia Bernasconi, Cristina Cappelletti, Francesca Navone, Valeria Nessi, Fulvio Baggi, Isabelle Vernos, Stefania Romaggi, Paolo Confalonieri, Marina Mora, Lucia Morandi, Renato Mantegazza

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

The idiopathic inflammatory myopathies (IIMs) dermatomyositis, polymyositis, and inclusion body myositis are characterized by myofiber degeneration and inflammation. The triggering factors of muscle autoaggression in these disorders are unknown, but infiltrating T cells may be activated locally and proliferate in situ. T-cell polarization involving reorientation of cytoskeleton and microtubule-organizing centers mediated by motor proteins may occur within inflammatory cells in the muscle. We therefore analyzed ubiquitous and neuronal kinesin superfamily (KIF) members KIF-5, dynein, and KIF4 in IIM muscle biopsies and in activated peripheral blood lymphocytes from healthy donors. Only KIF-4 was altered. Transcript levels were significantly higher in IIM muscle than in controls, and KIF4 inflammatory cells were found in IIM muscles. In polymyositis and inclusion body myositis, KIF4 cells were mainly located around individual muscle fibers, whereas in dermatomyositis, they were also near blood vessels. KIF4 cells were not specific to any immune lineage, and some were Ki67. In peripheral blood lymphocytes stimulated with mitogens, interleukin 2 or anti-CD3/CD28 antibodies, KIF4 expression was upregulated, and the protein was localized in the cytoplasm in association with lysosome-associated membrane protein 1 and perforin lysosomal vesicles. These results imply that KIF4 is associated with activated T cells, irrespective of their functional phenotype, and that it is likely involved in cytoskeletal modifications associated with in situ T-cell activation in IIM.

Original languageEnglish
Pages (from-to)624-632
Number of pages9
JournalJournal of Neuropathology and Experimental Neurology
Volume67
Issue number6
DOIs
Publication statusPublished - Jun 2008

Fingerprint

Kinesin
Myositis
Muscles
Inclusion Body Myositis
T-Lymphocytes
Dermatomyositis
Proteins
Lysosome-Associated Membrane Glycoproteins
Microtubule-Organizing Center
Lymphocytes
Dyneins
Polymyositis
Perforin
Cytoskeleton
Mitogens
Muscle Cells
Interleukin-2
Blood Vessels
Cytoplasm
Inflammation

Keywords

  • Inflammatory myopathies
  • KIF4
  • Kinesin
  • T-cell costimulation
  • T-cell proliferation

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neuroscience(all)

Cite this

The kinesin superfamily motor protein KIF4 is associated with immune cell activation in idiopathic inflammatory myopathies. / Bernasconi, Pia; Cappelletti, Cristina; Navone, Francesca; Nessi, Valeria; Baggi, Fulvio; Vernos, Isabelle; Romaggi, Stefania; Confalonieri, Paolo; Mora, Marina; Morandi, Lucia; Mantegazza, Renato.

In: Journal of Neuropathology and Experimental Neurology, Vol. 67, No. 6, 06.2008, p. 624-632.

Research output: Contribution to journalArticle

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