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 language | English |
|---|---|
| Pages (from-to) | 624-632 |
| Number of pages | 9 |
| Journal | Journal of Neuropathology and Experimental Neurology |
| Volume | 67 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - Jun 2008 |
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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 journal › Article
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TY - JOUR
T1 - The kinesin superfamily motor protein KIF4 is associated with immune cell activation in idiopathic inflammatory myopathies
AU - Bernasconi, Pia
AU - Cappelletti, Cristina
AU - Navone, Francesca
AU - Nessi, Valeria
AU - Baggi, Fulvio
AU - Vernos, Isabelle
AU - Romaggi, Stefania
AU - Confalonieri, Paolo
AU - Mora, Marina
AU - Morandi, Lucia
AU - Mantegazza, Renato
PY - 2008/6
Y1 - 2008/6
N2 - 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.
AB - 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.
KW - Inflammatory myopathies
KW - KIF4
KW - Kinesin
KW - T-cell costimulation
KW - T-cell proliferation
UR - http://www.scopus.com/inward/record.url?scp=44649151204&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=44649151204&partnerID=8YFLogxK
U2 - 10.1097/NEN.0b013e318177e5fd
DO - 10.1097/NEN.0b013e318177e5fd
M3 - Article
C2 - 18520780
AN - SCOPUS:44649151204
VL - 67
SP - 624
EP - 632
JO - American Journal of Psychotherapy
JF - American Journal of Psychotherapy
SN - 0002-9564
IS - 6
ER -