CD99 isoforms regulate CD1a expression in human monocyte-derived DCs through ATF-2/CREB-1 phosphorylation

Autor: Frédéric Larbret, Karim Mahiddine, Alain Bernard, Hanen Bziouech, Ghislaine Bernard, Aude Mallavialle
Přispěvatelé: Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Régulations des réactions immunitaires et inflammatoires, Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-IFR50-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre méditerranéen de médecine moléculaire (C3M), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Laboratoire Tolérance Immunitaire (TIM), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), Centre Hospitalier Universitaire de Nice (CHU Nice)
Jazyk: angličtina
Rok vydání: 2016
Předmět:
0301 basic medicine
MESH: Antigens
CD1
Transcription
Genetic
Nonclassical MHC
MESH: Protein Isoforms
MESH: Monocytes
Dendritic cells
Monocytes
alternative splicing-ATF2-CREB1
Small hairpin RNA
Antigens
CD1
0302 clinical medicine
Transcription (biology)
hemic and lymphatic diseases
Immunology and Allergy
Protein Isoforms
Phosphorylation
Cyclic AMP Response Element-Binding Protein
Cells
Cultured
biology
integumentary system
MESH: Dendritic Cells
Cell Differentiation
hemic and immune systems
MESH: Gene Expression Regulation
Cell biology
CD99
MESH: Cells
Cultured
MESH: Cyclic AMP Response Element-Binding Protein
Gene isoform
MESH: Cell Differentiation
Immunology
12E7 Antigen
CREB
Cell Line
03 medical and health sciences
MESH: Activating Transcription Factor 2
Humans
Transcription factor
MESH: Humans
Activating Transcription Factor 2
MESH: Phosphorylation
MESH: Transcription
Genetic
Alternative splicing
MESH: 12E7 Antigen
In vitro
MESH: Cell Line
030104 developmental biology
Gene Expression Regulation
biology.protein
Cancer research
[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
030215 immunology
Zdroj: European Journal of Immunology
European Journal of Immunology, Wiley-VCH Verlag, 2016, 46 (6), pp.1460-1471. ⟨10.1002/eji.201546143⟩
ISSN: 0014-2980
1521-4141
Popis: International audience; 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.
Databáze: OpenAIRE
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