A central role for transcription factor C/EBP-beta in regulating CD1d gene expression in human keratinocytes.
CD1d is a nonclassical Ag-presenting molecule that presents glycolipid Ags to NKT cells that are involved in immune defense and tumor rejection. It also plays a role in immunoregulatory functions in the epidermis. The mechanisms controlling the expression of CD1d are not well understood. Therefore, we cloned the CD1d gene promoter and characterized its activities in primary human keratinocytes and other cell lines of epithelial origin. We found that a CCAAT box in the CD1d promoter is required for its expression in keratinocytes. We show here that transcription factor C/EBP-beta binds to the CCAAT box in the CD1d promoter in vitro and in vivo. Consistent with these observations, deletion of the gene encoding for C/EBP-beta caused a loss of CD1d expression. The in vivo regulation of CD1d has significant implications for the pathologic mechanisms of certain immunologic skin diseases in which NKT cells play a role, such as allergic contact dermatitis and psoriasis. Together, these data show a central role for C/EBP-beta in regulating CD1d transcription.
Sikder
Hashmat
H
Department of Dermatology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Zhao
Yuming
Y
Balato
Anna
A
Chapoval
Andre
A
Fishelevich
Rita
R
Gade
Padmaja
P
Singh
Ishwar S
IS
Kalvakolanu
Dhananjaya V
DV
Johnson
Peter F
PF
Gaspari
Anthony A
AA
D055610:Antigens, CD1d / Q000235:genetics*; D001665:Binding Sites; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000502:physiology*; D002460:Cell Line; D003001:Cloning, Molecular; D004847:Epithelial Cells; D005786:Gene Expression Regulation; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism*; D055611:Natural Killer T-Cells; D011401:Promoter Regions, Genetic; D012871:Skin Diseases / Q000209:etiology / Q000276:immunology; D014158:Transcription, Genetic
D055610:Antigens, CD1d; D022782:CCAAT-Enhancer-Binding Protein-beta