Characterization of Foxp3 gene from grass carp (Ctenopharyngodon idellus): A rapamycin-inducible transcription factor in teleost immune system

In this study, we cloned grass carp foxp3 (gcfoxp3) gene including 5′ flanking region and determined its expression profiles in vivo under immunosuppressive conditions. Sequence analysis revealed that the promoter of gcfoxp3 contains AP-1, AML-1/Runx1, NF-κb and GATA-3 binding sites, which positively or negatively regulate mammalian foxp3 expression. In addition, the intron II of gcfoxp3 contains some putative binding sites including AP-1, NFAT, Smad3, RAR, CREB/ATF and FOXO1, which are corresponding to their locations in the proximal intronic enhancers of human foxp3. In an in vivo model of grass carp, an immunosuppressive agent rapamycin was showed to stimulate gcfoxp3 mRNA expression in thymus, gill, head kidney and spleen after bacterial challenge. Moreover, rapamycin increased gcFoxp3 protein levels with an additive manner in the infected fish. These findings support the involvement of fish Foxp3 in immune response and highlight a possible signaling pathway that regulates teleost Foxp3 expression.

► Transcription factor Foxp3 gene was identified from Ctenopharyngodon idellu.
► We analyzed the putative transcription factor binding sites in gcfoxp3 gene.
► Rapamycin stimulated gcfoxp3 mRNA expression in vivo after bacterial challenge.
► Rapamycin increased gcFoxp3 protein levels with an additive manner in infected fish.
► Like mammalian Foxp3, gcFoxp3 expression may be regulated by the target of rapamycin signaling pathway.