title: Abnormal intracellular distribution of NFAT1 in T lymphocytes from patients with systemic lupus erythematosus and characteristic clinical features.
abstract: Systemic lupus erythematosus (SLE) presents various clinical features; however, underlying mechanisms remain unclear. In the immunity of SLE, impaired T cell receptor (TCR) signaling and altered cytokine production are in the center of pathogenesis, although, little is known about NFAT (nuclear factor of activated T cells) in lupus T lymphocytes. TCR stimulation activates NFAT1 through Ca2+/calcineurin (Cn) pathway, facilitating nuclear translocation of NFAT1 from cytosol. Therefore, we investigated relationship of disease activity/features and intracellular NFAT1 localization in T lymphocytes from active lupus patients by fractionation. Results showed no significant relationship between disease activity and NFAT1 distribution. However, interestingly, we observed skewed NFAT1 distribution in pellet in patients with active lupus nephritis or pleuritis. In vitro cyclosporin A treatment suggested autonomously activated Ca2+/Cn pathway in lupus T lymphocytes. Considering these results, NFAT1 might be presenting the clinical heterogeneity in SLE.
authors.affiliation: The First Department of Internal Medicine, University of Occupational and Environmental Health, School of Medicine, 1-1 Iseigaoka, Yahatanishi, Kitakyushu, Fukuoka 807-8555, Japan. yukofuji@med.uoeh-u.ac.jp
authors.forename: Yuko
authors.initials: Y
authors.lastname: Fujii
authors.forename: Koichi
authors.initials: K
authors.lastname: Fujii
authors.forename: Shigeru
authors.initials: S
authors.lastname: Iwata
authors.forename: Katsunori
authors.initials: K
authors.lastname: Suzuki
authors.forename: Taeko
authors.initials: T
authors.lastname: Azuma
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Saito
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Tanaka
mesh_terms: D000328:Adult; D000368:Aged; D016572:Cyclosporine / Q000494:pharmacology; D005260:Female; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D050778:NFATC Transcription Factors / Q000378:metabolism*; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*
chemical_list: D020672:I-kappa B Proteins; D050778:NFATC Transcription Factors; C494006:NFATC2 protein, human; D016572:Cyclosporine