The Kinesin Superfamily Motor Protein KIF4 Is Associated With Immune Cell Activation in Idiopathic Inflammatory Myopathies (original) (raw)

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Pia Bernasconi, PhD ,

From the Neurology IV, Foundation Neurological Institute "Carlo Besta", Department of Medical Pharmacology, Milan, Italy (PB, CC, VN, FB, SR, PC, MM, LM, RM)

Send correspondence and reprint requests to: Pia Bernasconi, PhD, Neurology IV, Foundation Neurological Institute "Carlo Besta," Via Celoria 11, 20133 Milan, Italy; E-mail: [email protected]

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Cristina Cappelletti, PhD ,

Cristina Cappelletti, PhD

From the Neurology IV, Foundation Neurological Institute "Carlo Besta", Department of Medical Pharmacology, Milan, Italy (PB, CC, VN, FB, SR, PC, MM, LM, RM)

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Francesca Navone, MD ,

CNR Institute of Neuroscience, Cellular and Molecular Pharmacology Laboratory, Department of Medical Pharmacology, Milan, Italy (FN)

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Valeria Nessi, PhD ,

From the Neurology IV, Foundation Neurological Institute "Carlo Besta", Department of Medical Pharmacology, Milan, Italy (PB, CC, VN, FB, SR, PC, MM, LM, RM)

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Fulvio Baggi, PhD ,

From the Neurology IV, Foundation Neurological Institute "Carlo Besta", Department of Medical Pharmacology, Milan, Italy (PB, CC, VN, FB, SR, PC, MM, LM, RM)

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Isabelle Vernos, PhD ,

ICREA and Centro de Regulación Genómica, Cell and Developmental Biology Program, Barcelona, Spain (IV)

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Stefania Romaggi ,

From the Neurology IV, Foundation Neurological Institute "Carlo Besta", Department of Medical Pharmacology, Milan, Italy (PB, CC, VN, FB, SR, PC, MM, LM, RM)

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Paolo Confalonieri, MD ,

From the Neurology IV, Foundation Neurological Institute "Carlo Besta", Department of Medical Pharmacology, Milan, Italy (PB, CC, VN, FB, SR, PC, MM, LM, RM)

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Marina Mora, PhD ,

From the Neurology IV, Foundation Neurological Institute "Carlo Besta", Department of Medical Pharmacology, Milan, Italy (PB, CC, VN, FB, SR, PC, MM, LM, RM)

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Lucia Morandi, MD ,

From the Neurology IV, Foundation Neurological Institute "Carlo Besta", Department of Medical Pharmacology, Milan, Italy (PB, CC, VN, FB, SR, PC, MM, LM, RM)

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Pia Bernasconi, Cristina Cappelletti, Francesca Navone, Valeria Nessi, Fulvio Baggi, Isabelle Vernos, Stefania Romaggi, Paolo Confalonieri, Marina Mora, Lucia Morandi, Renato Mantegazza, The Kinesin Superfamily Motor Protein KIF4 Is Associated With Immune Cell Activation in Idiopathic Inflammatory Myopathies, Journal of Neuropathology & Experimental Neurology, Volume 67, Issue 6, June 2008, Pages 624–632, https://doi.org/10.1097/NEN.0b013e318177e5fd
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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.

Copyright © 2008 by the American Association of Neuropathologists, Inc.

Topic:

• phenotype
• polymyositis
• dermatomyositis
• inflammatory cells
• inflammation
• aldesleukin
• biopsy
• cd28 antigens
• cytoplasm
• cytoskeleton
• dynein atpase
• ki-67 antigen
• kinesin
• lymphocytes
• lysosomes
• membrane proteins
• microtubule-organizing center
• mitogens
• muscle fibers
• myositis, inclusion body
• rna, messenger
• t-lymphocytes
• idiopathic inflammatory myopathy
• antibodies
• vesicle
• immune cell activation
• t-cell activation
• molecular motor proteins
• perforin
• tissue degeneration
• donors

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