期刊
EUROPEAN JOURNAL OF IMMUNOLOGY
卷 46, 期 6, 页码 1460-1471出版社
WILEY-BLACKWELL
DOI: 10.1002/eji.201546143
关键词
alternative splicing-ATF2-CREB1; CD99; Dendritic cells; Nonclassical MHC
类别
资金
- INSERM
- Association pour la Recherche sur le Cancer (ARC)
- Universite de Nice-Sophia-Antipolis
- European Project: Prognosis and Therapeutic target in the Ewing Family of Tumors (PROTHETS)
- Institut National du Cancer (INCA) Canceropole PACA
- Fondation Princesse Grace de Monaco
- Ministere de la Recherche
- TxCell
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.
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