GATA1-Deficient Dendritic Cells Display Impaired CCL21-Dependent Migration toward Lymph Nodes Due to Reduced Levels of Polysialic Acid.
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-KODCmice. Migration assays performed in vitro showed that this defect was selective for CCL21, but not CCL19. Interestingly, we show that Gata1-KODCDCs have reduced polysialic acid levels on their surface, which is a known determinant for the proper migration of DCs toward CCL21.
Department of Blood Cell Research, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam 1066CX, the Netherlands.
Maaike R
MR
Scheenstra
Department of Blood Cell Research, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam 1066CX, the Netherlands.
Iris M
0000-0001-8862-8000
IM
De Cuyper
Laboratory of Immunoregulation, VIB, Ghent 9052, Belgium.|Department of Internal Medicine, Ghent University, Ghent 9000, Belgium.
Filipe
0000-0001-5245-9735
F
Branco-Madeira
Data Mining and Modeling for Biomedicine, Department of Biomedical Molecular Biology, VIB Inflammation Research Center, Ghent University, Ghent 9052, Belgium.
Pieter
0000-0003-4762-8770
P
de Bleser
Laboratory of Immunoregulation, VIB, Ghent 9052, Belgium.
Mirjam
0000-0003-1436-3876
M
Kool
Department of Blood Cell Research, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam 1066CX, the Netherlands.
Marjolein
0000-0002-7124-0832
M
Meinders
Department of Molecular Cell Biology, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam 1066CX, the Netherlands.
Mark
M
Hoogenboezem
Department of Molecular Cell Biology, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam 1066CX, the Netherlands.
Erik
0000-0002-8234-9972
E
Mul
Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam 1066CX, the Netherlands.
Monika C
0000-0003-3242-1363
MC
Wolkers
Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam 1066CX, the Netherlands.
Fiamma
0000-0003-1634-947X
F
Salerno
Department of Blood Cell Research, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam 1066CX, the Netherlands.
Benjamin
0000-0001-7500-5760
B
Nota
Data Mining and Modeling for Biomedicine, Department of Biomedical Molecular Biology, VIB Inflammation Research Center, Ghent University, Ghent 9052, Belgium.
Yvan
0000-0002-0415-1506
Y
Saeys
Experimental Animal Pathology, The Netherlands Cancer Institute, Amsterdam 1066CX, the Netherlands.
Sjoerd
0000-0002-1891-1940
S
Klarenbeek
Center for Biomics, Erasmus MC, Rotterdam 3015 CN, the Netherlands.
Wilfred F J
0000-0002-0421-8301
WF
van IJcken
Laboratory of Immunoregulation, VIB, Ghent 9052, Belgium.|Department of Internal Medicine, Ghent University, Ghent 9000, Belgium.
Hamida
H
Hammad
Department of Cell Biology, Erasmus MC, Rotterdam 3015 CN, the Netherlands.
Sjaak
0000-0002-3690-1201
S
Philipsen
Department of Blood Cell Research, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam 1066CX, the Netherlands.
Timo K
TK
van den Berg
Department of Blood Cell Research, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam 1066CX, the Netherlands.|Department of Pediatric Hematology, Immunology and Infectious Disease, Emma Children's Hospital, Academic Medical Center, University of Amsterdam, Amsterdam 1105AZ, the Netherlands.
Taco W
TW
Kuijpers
Laboratory of Immunoregulation, VIB, Ghent 9052, Belgium.|Department of Internal Medicine, Ghent University, Ghent 9000, Belgium.|Department of Pulmonary Medicine, Erasmus MC, Rotterdam 3015 CN, the Netherlands; and.
Bart N
BN
Lambrecht
Department of Blood Cell Research, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam 1066CX, the Netherlands; lgutierrezg@salud.madrid.org.|Departamento de Hematología, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria San Carlos, Madrid 28040, Spain.
Laura
0000-0001-8443-900X
L
Gutiérrez
D000818:Animals; D002465:Cell Movement / Q000235:genetics / Q000276:immunology*; D054415:Chemokine CCL19 / Q000235:genetics / Q000276:immunology; D054421:Chemokine CCL21 / Q000235:genetics / Q000276:immunology*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D050982:GATA1 Transcription Factor / Q000172:deficiency / Q000276:immunology*; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D012794:Sialic Acids / Q000235:genetics / Q000276:immunology*
C515461:Ccl19 protein, mouse; D054415:Chemokine CCL19; D054421:Chemokine CCL21; D050982:GATA1 Transcription Factor; C494689:Gata1 protein, mouse; D012794:Sialic Acids; C021319:polysialic acid