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GATA1-Deficient Dendritic Cells Display Impaired CCL21-Dependent Migration toward Lymph Nodes Due to Reduced Levels of Polysialic Acid
Author(s) -
Maaike R. Scheenstra,
Iris M. De Cuyper,
Filipe BrancoMadeira,
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
Publication year - 2016
Publication title -
the journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.737
H-Index - 372
eISSN - 1550-6606
pISSN - 0022-1767
DOI - 10.4049/jimmunol.1600103
Subject(s) - gata1 , ccl19 , dendritic cell , ccl21 , microbiology and biotechnology , polysialic acid , immune system , biology , cell migration , immunology , chemistry , haematopoiesis , chemokine , cell , cell adhesion , stem cell , neural cell adhesion molecule , genetics , chemokine receptor
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 DC ), 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 DC mice. Migration assays performed in vitro showed that this defect was selective for CCL21, but not CCL19. Interestingly, we show that Gata1-KO DC DCs have reduced polysialic acid levels on their surface, which is a known determinant for the proper migration of DCs toward CCL21.

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