Nuclear receptors in human immune cells: expression and correlations.

Nuclear receptors (NR) are key modulators of gene transcription. Their activity is ligand induced and modulates a large variety of tissue-specific cellular functions. However, for many NR little is known about their role in cells of the immune system. In this study, expression patterns and distribution of 24 NR were investigated in human peripheral blood mononuclear cells. We provide the first evidence of the expression of the 12 receptors CAR, CoupTFalpha, CoupTFbeta, FXR, GCNF, HNF4alpha, PPARbeta/delta, PXR, RevErbbeta, TR2, TR4 and TLX in highly purified CD4, CD8, CD19, CD14 cells. The expression profile of RevErbalpha and LXRalpha previously observed in B cell and macrophages, respectively, has been extended to CD4, CD8 and CD14 cells. Except for RARbeta, which was absence in any of the cells tested, our results suggest an almost ubiquitous expression of the NR in the different cell lineages of the immune system. The expression of CAR, CoupTFalpha, FXR was also confirmed at a protein level and despite conspicuous mRNA levels of HNF4alpha, only low levels of this receptor were detectable in the nuclear fraction of PBMCs. Expression of the latter receptors was mostly only a fraction (4-20%) of their expression in the thyroid gland, the adrenal gland, the lung or subcutaneous adipose tissue. The Spearman rank order correlation test was performed to examine the correlation in expression between individual nuclear receptor pairs in the four cell types for several donors. Distinct correlation patterns were observed between receptor pairs in the individual cell types. In CD4 T cells four NR, GCNF, PPARgamma, PPARalpha7 and RevErbbeta are perfectly correlated with each other (P> or =0.0167). In the other cell types correlations between NR pairs were more diverse, but also statistically highly significant. Interestingly, the relative expression level of a number of receptor pairs ranked identical or similar in at least three (CoupTFalpha and PPARbeta/delta, CoupTFbeta and HNF4alpha as well as RORbeta and PXR) or four cell types (CoupTFalpha and CoupTFbeta, PPARgamma and RevErbbeta). Despite the variability of NR expression in immune cells, these results suggest that some of the NR may be co-regulated in human immune cells.