Abstract
The TNFR2 receptor is expressed by highly active regulatory T cells, and thus constitutes an important therapeutic target for the treatment of autoimmune disease and cancer. Disease susceptibility as well as the potential response to therapies directed at TNFR2 could be significantly impacted by genetic variation in the promoter of the TNFRSF1B gene that codes for the TNFR2 protein. To date, only a few studies have examined the association of TNFRSF1B promoter variation with disease, and the potential impact on T-regulatory cell (Treg) number and function has not been examined. We propose that copy number variation of a key transcription factor binding site has a significant effect on TNFRSF1B promoter activity, and should be considered in studies of disease susceptibility and especially with regard to variation in the level of TNFR2 expression on Tregs.
Highlights
Tumor necrosis factor (TNF) is a multifunctional cytokine that can affect multiple cellular responses, such as inflammation, tumorigenesis, viral replication, septic shock, and autoimmunity [1]
Genetic variation in the TNFR2 receptor has been associated with several human diseases, we believe that additional studies examining variation in the copy number of the variable number tandem repeat (VNTR) bearing a predicted SP1-binding site in the TNFRSF1B promoter region are warranted
We have shown that there is a direct functional effect on promoter activity and transcript levels, which would be predicted to affect receptor levels
Summary
Tumor necrosis factor (TNF) is a multifunctional cytokine that can affect multiple cellular responses, such as inflammation, tumorigenesis, viral replication, septic shock, and autoimmunity [1]. Changes in TNFR2 levels were associated with disease susceptibility, none of the studies cited above looked directly at variation within the TNFRSF1B promoter region. The repeated sequence contains a predicted SP1-binding site, and the number of repeats might have an effect on promoter activity.
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