The kinesin superfamily motor protein KIF4 is associated with immune cell activation in idiopathic inflammatory myopathies.
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.
Bernasconi
Pia
P
Neurology IV, Foundation Neurological Institute Carlo Besta, Department of Medical Pharmacology, Milan, Italy. pbernasconi@instituto-besta.it
Cappelletti
Cristina
C
Navone
Francesca
F
Nessi
Valeria
V
Baggi
Fulvio
F
Vernos
Isabelle
I
Romaggi
Stefania
S
Confalonieri
Paolo
P
Mora
Marina
M
Morandi
Lucia
L
Mantegazza
Renato
R
D000328:Adult; D015153:Blotting, Western; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016547:Kinesins / Q000096:biosynthesis*; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D018613:Microscopy, Confocal; D018482:Muscle, Skeletal / Q000276:immunology / Q000378:metabolism; D009220:Myositis / Q000276:immunology* / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology*; D014158:Transcription, Genetic
D012333:RNA, Messenger; D016547:Kinesins