CD99 isoforms regulate CD1a expression in human monocyte-derived DCs through ATF-2/CREB-1 phosphorylation.
CD1a expression is considered one of the major characteristics qualifying in vitro human dendritic cells (DCs) during their generation process. Here, we report that CD1A transcription is regulated by a mechanism involving the long and short isoforms of CD99. Using a lentiviral construct encoding for a CD99 short hairpin RNA, we were able to inhibit CD99 expression in human primary DCs. In such cells, CD1a membrane expression increased and CD1A transcripts were much higher in abundance compared to cells expressing CD99 long form (CD99LF). We also show that CD1A transcription is accompanied by a switch in expression from CD99LF to expression at comparable levels of both CD99 isoforms during immature DCs generation in vitro. We demonstrate that CD99LF maintains a lower level of CD1A transcription by up-regulating the phosphorylated form of the ATF-2 transcription factor and that CD99 short form (SF) is required to counteract this regulatory mechanism. Elucidation of the molecular mechanisms related to CD99 alternative splicing will be very helpful to better understand the transcriptional regulatory mechanism of CD1a molecules during DCs differentiation and its involvement in the immune response.
INSERM U 576-Nice, France.|Université de Nice Sophia Antipolis, Nice, France.|INSERM U1043, CNRS, UMR5282 Centre de Physiopathologie de Toulouse Purpan, Université Toulouse III Paul-Sabatier, Toulouse, France.
Karim
K
Mahiddine
INSERM U 576-Nice, France.|Université de Nice Sophia Antipolis, Nice, France.|INSERM, U1065 Centre Méditerranéen de Médecine Moléculaire (C3M), Nice, France.
Aude
A
Mallavialle
INSERM U 576-Nice, France.|Université de Nice Sophia Antipolis, Nice, France.
Hanen
H
Bziouech
INSERM U 576-Nice, France.|Université de Nice Sophia Antipolis, Nice, France.|EA 6302, Tolérance Immunitaire Université de Nice Hôpital de l'Archet, Nice cedex 3, France.
Frédéric
F
Larbret
INSERM U 576-Nice, France.|Université de Nice Sophia Antipolis, Nice, France.|Laboratoire d'Immunologie CHU de Nice, Nice, France.
Alain
A
Bernard
INSERM U 576-Nice, France.|Université de Nice Sophia Antipolis, Nice, France.|Laboratoire d'Immunologie CHU de Nice, Nice, France.
Ghislaine
G
Bernard
D000071443:12E7 Antigen / Q000235:genetics / Q000378:metabolism*; D051698:Activating Transcription Factor 2 / Q000378:metabolism*; D018949:Antigens, CD1 / Q000235:genetics* / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D002478:Cells, Cultured; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D009000:Monocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D010766:Phosphorylation; D020033:Protein Isoforms; D014158:Transcription, Genetic
D000071443:12E7 Antigen; D051698:Activating Transcription Factor 2; D018949:Antigens, CD1; C419393:CD1a antigen; C115163:CREB1 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; D020033:Protein Isoforms
CD99; Dendritic cells; Nonclassical MHC; alternative splicing-ATF2-CREB1