Retinoic acid regulates CD1d gene expression at the transcriptional level in human and rodent monocytic cells.
CD1d belongs to a group of nonclassical antigen-presenting molecules that present glycolipid antigens and thereby activate natural killer T (NKT) cells, a subset of bifunctional T cells. Little is known so far regarding the expression and physiologic regulation of CD1d. Here we show that all-trans-retinoic acid (RA), the active metabolite of vitamin A, rapidly (1 hr after treatment) increases CD1d mRNA in human and rodent monocytic cells at a physiologic dose (10 nM). The induction is RA specific and RA receptor (RAR) dependent-RA and an RARalpha agonist, Am580, both had a pronounced positive effect, whereas the addition of RARalpha antagonist partially blocked the increase in CD1d mRNA induced by RA and Am580. The induction was also completely blocked by the presence of actinomycin D. A putative RA-response element was identified in the distal 5' flanking region of the CD1d gene, which binds nuclear retinoid receptors and was responsive to RA in both gel mobility shift assay and transient transfection assay in THP-1 cells. These results further confirmed the transcriptional regulation of RA in CD1d gene expression. Moreover, RA significantly increased alpha-galactosylceramide-induced spleen cell proliferation. These studies together provide evidence for a previously unknown mechanism of CD1d gene expression regulation by RA and suggest that RA is a significant modulator of NKT cell activation.
Chen
Qiuyan
Q
Department of Nutritional Sciences, Pennsylvania State University, 126-S Henderson Building, University Park, PA 16802, USA.
Ross
A Catharine
AC
D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects / Q000276:immunology; D018949:Antigens, CD1 / Q000096:biosynthesis* / Q000276:immunology; D055610:Antigens, CD1d; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D003609:Dactinomycin / Q000494:pharmacology; D005699:Galactosylceramides / Q000276:immunology / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000276:immunology; D006017:Glycolipids / Q000276:immunology; D018922:HL-60 Cells; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000378:metabolism*; D008297:Male; D051379:Mice; D012333:RNA, Messenger / Q000096:biosynthesis / Q000276:immunology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018168:Receptors, Retinoic Acid / Q000096:biosynthesis / Q000276:immunology; D020218:Response Elements / Q000187:drug effects / Q000276:immunology; D000072482:Retinoic Acid Receptor alpha; D013154:Spleen / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects* / Q000276:immunology; D014212:Tretinoin / Q000494:pharmacology*; D020298:U937 Cells
D018949:Antigens, CD1; D055610:Antigens, CD1d; D000970:Antineoplastic Agents; D001565:Benzoates; C526877:CD1D protein, human; D005699:Galactosylceramides; D006017:Glycolipids; C000607071:RARA protein, human; D012333:RNA, Messenger; C000607072:Rara protein, mouse; C000607073:Rara protein, rat; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D013764:Tetrahydronaphthalenes; C068073:Am 580; D003609:Dactinomycin; D014212:Tretinoin