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

Maaike R Scheenstra ,
Iris M De Cuyper ,
Filipe Branco-Madeira ,
Pieter de Bleser ,
Mirjam Kool ,
Marjolein Meinders ,
Mark Hoogenboezem ,
Erik Mul ,
Monika C Wolkers ,
Fiamma Salerno ,
Benjamin Nota ,
Yvan Saeys ,
Sjoerd Klarenbeek ,
Wilfred F J van IJcken ,
Hamida Hammad ,
Sjaak Philipsen ,
Timo K van den Berg ,
Taco W Kuijpers ,
Bart N Lambrecht ,
Laura Gutiérrez

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-KODC), 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-KODC mice. Migration assays performed in vitro showed that this defect was selective for CCL21, but not CCL19. Interestingly, we show that Gata1-KODC DCs have reduced polysialic acid levels on their surface, which is a known determinant for the proper migration of DCs toward CCL21.

More about this publication

Journal of immunology (Baltimore, Md. : 1950)

Volume 197
Issue nr. 11
Pages 4312-4324
Publication date 01-12-2016

Full text links

Publisher website (DOI) 10.4049/jimmunol.1600103
Europe PubMed Central 27815426
Pubmed 27815426

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