The 2011 Noble Prize in Physiology or Medicine was awarded to Bruce A. Beutler, Jules A. Hoffmann and Ralph M. Steinman for their groundbreaking research within immunology. Bruce A. Beutler and Jules A. Hoffmann were recognized for their discoveries on Toll and Toll‐like receptor activation of innate immunity in fruit fly and mammals, respectively. Ralph M. Steinman received the award for the discovery of dendritic cells, a cell type bridging innate and adaptive immunity, and how these cells orchestrate immune responses.

Dendritic cells (DC) are the only hematopoietic cells expressing the epithelial specific Ets transcription factor ESE-3. Here we analyzed presence and quantity of isoforms ESE-3a, ESE-3b and ESE-3j in various immunogenic and tolerogenic human monocyte-derived DC (moDC) and blood DC populations using quantitative real time PCR and immunoblot analyses. ESE-3a and ESE-3b were detectable in all moDC populations with ESE-3b being the main transcript. ESE-3b expression was upregulated in immunogenic moDC and downregulated in tolerogenic moDC compared to immature moDC. ESE-3a had similar transcript levels in immature and immunogenic moDC and had very low levels in tolerogenic moDC. In blood DC populations only splice variant ESE-3b was detectable. ESE-3j was not detectable in any of the DC populations. These findings suggest that ESE-3b is the functionally most important ESE-3 isoform in DC.

The transcription factor ESE-3 has been suggested to be involved in regulating the immunogenicity of human monocyte-derived dendritic cells (moDCs). While ESE-3 is not expressed in monocytes, it is upregulated during the differentiation of monocytes into dendritic cells (DCs) and highly expressed in immunogenic DCs while downregulated in tolerogenic DCs. Activation of peroxisome proliferator-activated receptor gamma (PPAR-c) during DC development has been shown to result in a rather tolerogenic cell population. In this study, we identified eight PPAR-c binding sites upstream of the ESE-3 gene. Activation of the PPAR-c pathway with synthetic PPAR-c ligands during moDC generation resulted in upregulation of ESE-3b expression on mRNA and protein level, phenotypic alterations and reduced capacity of the cells to stimulate allogeneic T cells. This could be inhibited by blocking the PPAR-c pathway with specific antagonists. Our results suggest PPAR-c to be involved in the regulation of ESE-3b expression during moDC development and that ESE-3 expression is not correlated with the immunogenicity of DCs.