Transcriptional regulation of mouse delta-opioid receptor gene in T cells

δ-Opioid receptors (DOR) present on T cells have been shown to mediate the immunomodulatory effects of endogenous and synthetic DOR agonists on T cells. Considerable evidence indicates that the transcription of DOR gene is correlated with both the expression of DOR on T cells and the capacity of DOR agonists to modulate the immunological functions of the T cell. To uncover the molecular mechanism underlying the transcriptional regulation of DOR gene in T cells, we analyzed a 1.3-kb DNA fragment immediately upstream of the translation start site (−1300 to +1 bp, with the translation start site designated as +1) of mouse DOR gene in mouse T cell lines that constitutively expresses DOR. Through both in vivo and in vitro experiments, we have demonstrated that Ikaros (Ik)-2 homodimers bind to an Ik-binding site (−378 to −374) and exert a position-dependent trans-activation effect on the DOR promoter in T cells. Moreover, an E box (−185 to −180) that binds upstream stimulatory factor is essential for the DOR promoter activity in both resting and activated T cells. Furthermore, we have demonstrated that Ik-2 and upstream stimulatory factor synergize in trans-activating the DOR promoter in T cells via the putative Ik-binding site and the E box, respectively.