Increased levels of NF-ATc2 differentially regulate CD154 and IL-2 genes in T cells from patients with systemic lupus erythematosus.
T cells from patients with systemic lupus erythematosus (SLE) are characterized by heightened TCR-initiated free intracytoplasmic calcium responses. We demonstrate that activated T cells from SLE patients, but not from rheumatoid arthritis patients, displayed higher levels of the calcineurin-dependent transcription factor NF-ATc2 in the nucleus compared with control T cells. DNA NF-AT-binding activity was also increased, as was the amount of NF-ATc2 bound to the promoters of CD154 (CD40L) and IL-2 genes. Nevertheless, although high NF-ATc2 levels translated into higher CD154 transcription in SLE, IL-2 transcription was decreased. The absence of important transcriptional activators (AP-1, NF-kappaBeta) and the presence of transcriptional repressors (cAMP response element modulator) on the IL-2 promoter explain this dichotomous effect.
Kyttaris
Vasileios C
VC
Department of Cellular Injury, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
Wang
Ying
Y
Juang
Yuang-Taung
YT
Weinstein
Arthur
A
Tsokos
George C
GC
D021581:Active Transport, Cell Nucleus; D000328:Adult; D023201:CD40 Ligand / Q000235:genetics*; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008213:Lymphocyte Activation; D008875:Middle Aged; D050778:NFATC Transcription Factors / Q000235:genetics / Q000502:physiology*; D011401:Promoter Regions, Genetic; D013601:T-Lymphocytes / Q000276:immunology*; D014157:Transcription Factors; D014158:Transcription, Genetic / Q000276:immunology; D015854:Up-Regulation
D007376:Interleukin-2; D050778:NFATC Transcription Factors; C494006:NFATC2 protein, human; D014157:Transcription Factors; D023201:CD40 Ligand