GATA1-Deficient Dendritic Cells Display Impaired CCL21-Dependent Migration toward Lymph Nodes Due to Reduced Levels of Polysialic Acid
Year: 2016
Type: article
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.
Source: The Journal of Immunology
Authors: 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
Institutions: Amsterdam UMC Location University of Amsterdam, Sanquin, University of Amsterdam, Vlaams Instituut voor Biotechnologie, Ghent University, VIB-UGent Center for Inflammation Research, The Netherlands Cancer Institute, Erasmus MC, Emma Kinderziekenhuis, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2547023596