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GATA1-Deficient Dendritic Cells Display Impaired CCL21-Dependent Migration toward Lymph Nodes Due to Reduced Levels of Polysialic Acid.

Authors :
Scheenstra MR
De Cuyper IM
Branco-Madeira F
de Bleser P
Kool M
Meinders M
Hoogenboezem M
Mul E
Wolkers MC
Salerno F
Nota B
Saeys Y
Klarenbeek S
van IJcken WF
Hammad H
Philipsen S
van den Berg TK
Kuijpers TW
Lambrecht BN
GutiƩrrez L
Source :
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2016 Dec 01; Vol. 197 (11), pp. 4312-4324. Date of Electronic Publication: 2016 Nov 04.
Publication Year :
2016

Abstract

Dendritic cells (DCs) play a pivotal role in the regulation of the immune response. DC development and activation is finely orchestrated through transcriptional programs. GATA1 transcription factor is required for murine DC development, and data suggest that it might be involved in the fine-tuning of the life span and function of activated DCs. We generated DC-specific Gata1 knockout mice (Gata1-KO <superscript>DC</superscript> ), which presented a 20% reduction of splenic DCs, partially explained by enhanced apoptosis. RNA sequencing analysis revealed a number of deregulated genes involved in cell survival, migration, and function. DC migration toward peripheral lymph nodes was impaired in Gata1-KO <superscript>DC</superscript> mice. Migration assays performed in vitro showed that this defect was selective for CCL21, but not CCL19. Interestingly, we show that Gata1-KO <superscript>DC</superscript> DCs have reduced polysialic acid levels on their surface, which is a known determinant for the proper migration of DCs toward CCL21.<br /> (Copyright © 2016 by The American Association of Immunologists, Inc.)

Details

Language :
English
ISSN :
1550-6606
Volume :
197
Issue :
11
Database :
MEDLINE
Journal :
Journal of immunology (Baltimore, Md. : 1950)
Publication Type :
Academic Journal
Accession number :
27815426
Full Text :
https://doi.org/10.4049/jimmunol.1600103