title: Differential calcium signaling and Kv1.3 trafficking to the immunological synapse in systemic lupus erythematosus.
abstract: Systemic lupus erythematosus (SLE) T cells exhibit several activation signaling anomalies including defective Ca(2+) response and increased NF-AT nuclear translocation. The duration of the Ca(2+) signal is critical in the activation of specific transcription factors and a sustained Ca(2+) response activates NF-AT. Yet, the distribution of Ca(2+) responses in SLE T cells is not known. Furthermore, the mechanisms responsible for Ca(2+) alterations are not fully understood. Kv1.3 channels control Ca(2+) homeostasis in T cells. We reported a defect in Kv1.3 trafficking to the immunological synapse (IS) of SLE T cells that might contribute to the Ca(2+) defect. The present study compares single T cell quantitative Ca(2+) responses upon formation of the IS in SLE, normal, and rheumatoid arthritis (RA) donors. Also, we correlated cytosolic Ca(2+) concentrations and Kv1.3 trafficking in the IS by two-photon microscopy. We found that sustained [Ca(2+)](i) elevations constitute the predominant response to antigen stimulation of SLE T cells. This defect is selective to SLE as it was not observed in RA T cells. Further, we observed that in normal T cells termination of Ca(2+) influx is accompanied by Kv1.3 permanence in the IS, while Kv1.3 premature exit from the IS correlates with sustained Ca(2+) responses in SLE T cells. Thus, we propose that Kv1.3 trafficking abnormalities contribute to the altered distribution in Ca(2+) signaling in SLE T cells. Overall these defects may explain in part the T cell hyperactivity and dysfunction documented in SLE patients.
authors: Department of Internal Medicine, University of Cincinnati, OH 45267, USA.
authors: Stella A
authors: SA
authors: Nicolaou
authors: Lisa
authors: L
authors: Neumeier
authors: Koichi
authors: K
authors: Takimoto
authors: Susan Molleran
authors: SM
authors: Lee
authors: Heather J
authors: HJ
authors: Duncan
authors: Shashi K
authors: SK
authors: Kant
authors: Anne Barbara
authors: AB
authors: Mongey
authors: Alexandra H
authors: AH
authors: Filipovich
authors: Laura
authors: L
authors: Conforti
mesh_terms: D000328:Adult; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D020013:Calcium Signaling / Q000187:drug effects / Q000276:immunology*; D002461:Cell Line, Transformed; D005260:Female; D006801:Humans; D054992:Immunological Synapses / Q000276:immunology; D051664:Kv1.3 Potassium Channel / Q000276:immunology / Q000378:metabolism*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects / Q000502:physiology; D008297:Male; D008875:Middle Aged; D026902:Potassium Channel Blockers / Q000494:pharmacology; D021381:Protein Transport / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
chemical_list: D051664:Kv1.3 Potassium Channel; D026902:Potassium Channel Blockers