T cells from patients with systemic lupus erythematosus (SLE) have high levels of cAMP response element modulator (CREM)-alpha which bind to the interleukin (IL-2) promoter and limit IL-2 production. In this case-controlled study, we show that CREM-alpha mRNA levels were higher in T cells from patients with SLE than controls while CREB mRNA levels did not differ between the two groups. CREM-alpha mRNA levels did not correlate with clinical characteristics, disease activity or treatment. Nevertheless, there was a trend for patients on high doses of corticosteroids to have low levels of CREM-alpha mRNA. The discovery of specific non-toxic medications that block the expression of CREM-alpha may prove useful in reversing the aberrant T cell function in SLE.
T helper (Th)17 cells constitute a distinct subset of CD4 þ helper T cells that is mainly characterized by abundant interleukin (IL)-17 production and is involved in the host defence against bacteria and fungi as well as in the pathogenesis of autoimmune diseases. The retinoic orphan receptor (ROR)gt directs the transcriptional activation of the IL17 gene. Here, we report the presence of a novel RORgt isoform, RORgt-D(5 --8), which lacks the hinge-encoding exons 5 --8 and represses potently IL17 and IL21 gene transcription. It thereby reduces the expression of multiple Th17-assigned cytokines. We propose that RORgt-D(5 --8) acts as a dominant-negative regulator of RORgt-mediated gene regulation and the balance between the full-length RORgt and the novel repressor isoform may arbitrate IL-17 production in human T cells.
Systemic lupus erythematosus (SLE) is a clinically heterogeneous disease diagnosed on the presence of a constellation of clinical and laboratory findings. At the pathogenetic level,
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