PMID- 27815426 OWN - NLM STAT- MEDLINE DCOM- 20170726 LR - 20180124 IS - 1550-6606 (Electronic) IS - 0022-1767 (Linking) VI - 197 IP - 11 DP - 2016 Dec 1 TI - GATA1-Deficient Dendritic Cells Display Impaired CCL21-Dependent Migration toward Lymph Nodes Due to Reduced Levels of Polysialic Acid. PG - 4312-4324 AB - 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. CI - Copyright (c) 2016 by The American Association of Immunologists, Inc. FAU - Scheenstra, Maaike R AU - Scheenstra MR AD - Department of Blood Cell Research, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam 1066CX, the Netherlands. FAU - De Cuyper, Iris M AU - De Cuyper IM AUID- ORCID: 0000-0001-8862-8000 AD - Department of Blood Cell Research, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam 1066CX, the Netherlands. FAU - Branco-Madeira, Filipe AU - Branco-Madeira F AUID- ORCID: 0000-0001-5245-9735 AD - Laboratory of Immunoregulation, VIB, Ghent 9052, Belgium. AD - Department of Internal Medicine, Ghent University, Ghent 9000, Belgium. FAU - de Bleser, Pieter AU - de Bleser P AUID- ORCID: 0000-0003-4762-8770 AD - Data Mining and Modeling for Biomedicine, Department of Biomedical Molecular Biology, VIB Inflammation Research Center, Ghent University, Ghent 9052, Belgium. FAU - Kool, Mirjam AU - Kool M AUID- ORCID: 0000-0003-1436-3876 AD - Laboratory of Immunoregulation, VIB, Ghent 9052, Belgium. FAU - Meinders, Marjolein AU - Meinders M AUID- ORCID: 0000-0002-7124-0832 AD - Department of Blood Cell Research, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam 1066CX, the Netherlands. FAU - Hoogenboezem, Mark AU - Hoogenboezem M AD - Department of Molecular Cell Biology, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam 1066CX, the Netherlands. FAU - Mul, Erik AU - Mul E AUID- ORCID: 0000-0002-8234-9972 AD - Department of Molecular Cell Biology, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam 1066CX, the Netherlands. FAU - Wolkers, Monika C AU - Wolkers MC AUID- ORCID: 0000-0003-3242-1363 AD - Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam 1066CX, the Netherlands. FAU - Salerno, Fiamma AU - Salerno F AUID- ORCID: 0000-0003-1634-947X AD - Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam 1066CX, the Netherlands. FAU - Nota, Benjamin AU - Nota B AUID- ORCID: 0000-0001-7500-5760 AD - Department of Blood Cell Research, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam 1066CX, the Netherlands. FAU - Saeys, Yvan AU - Saeys Y AUID- ORCID: 0000-0002-0415-1506 AD - Data Mining and Modeling for Biomedicine, Department of Biomedical Molecular Biology, VIB Inflammation Research Center, Ghent University, Ghent 9052, Belgium. FAU - Klarenbeek, Sjoerd AU - Klarenbeek S AUID- ORCID: 0000-0002-1891-1940 AD - Experimental Animal Pathology, The Netherlands Cancer Institute, Amsterdam 1066CX, the Netherlands. FAU - van IJcken, Wilfred F J AU - van IJcken WF AUID- ORCID: 0000-0002-0421-8301 AD - Center for Biomics, Erasmus MC, Rotterdam 3015 CN, the Netherlands. FAU - Hammad, Hamida AU - Hammad H AD - Laboratory of Immunoregulation, VIB, Ghent 9052, Belgium. AD - Department of Internal Medicine, Ghent University, Ghent 9000, Belgium. FAU - Philipsen, Sjaak AU - Philipsen S AUID- ORCID: 0000-0002-3690-1201 AD - Department of Cell Biology, Erasmus MC, Rotterdam 3015 CN, the Netherlands. FAU - van den Berg, Timo K AU - van den Berg TK AD - Department of Blood Cell Research, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam 1066CX, the Netherlands. FAU - Kuijpers, Taco W AU - Kuijpers TW AD - Department of Blood Cell Research, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam 1066CX, the Netherlands. AD - Department of Pediatric Hematology, Immunology and Infectious Disease, Emma Children's Hospital, Academic Medical Center, University of Amsterdam, Amsterdam 1105AZ, the Netherlands. FAU - Lambrecht, Bart N AU - Lambrecht BN AD - Laboratory of Immunoregulation, VIB, Ghent 9052, Belgium. AD - Department of Internal Medicine, Ghent University, Ghent 9000, Belgium. AD - Department of Pulmonary Medicine, Erasmus MC, Rotterdam 3015 CN, the Netherlands; and. FAU - Gutierrez, Laura AU - Gutierrez L AUID- ORCID: 0000-0001-8443-900X AD - Department of Blood Cell Research, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam 1066CX, the Netherlands; lgutierrezg@salud.madrid.org. AD - Departamento de Hematologia, Hospital Clinico San Carlos, Instituto de Investigacion Sanitaria San Carlos, Madrid 28040, Spain. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20161104 PL - United States TA - J Immunol JT - Journal of immunology (Baltimore, Md. : 1950) JID - 2985117R RN - 0 (Ccl19 protein, mouse) RN - 0 (Chemokine CCL19) RN - 0 (Chemokine CCL21) RN - 0 (GATA1 Transcription Factor) RN - 0 (Gata1 protein, mouse) RN - 0 (Sialic Acids) RN - 0 (polysialic acid) SB - IM MH - Animals MH - Cell Movement/genetics/*immunology MH - Chemokine CCL19/genetics/immunology MH - Chemokine CCL21/genetics/*immunology MH - Dendritic Cells/cytology/*immunology MH - GATA1 Transcription Factor/deficiency/*immunology MH - Lymph Nodes/cytology/*immunology MH - Mice MH - Mice, Knockout MH - Sialic Acids/genetics/*immunology EDAT- 2016/11/07 06:00 MHDA- 2017/07/27 06:00 CRDT- 2016/11/06 06:00 PHST- 2016/01/21 00:00 [received] PHST- 2016/09/29 00:00 [accepted] PHST- 2016/11/07 06:00 [pubmed] PHST- 2017/07/27 06:00 [medline] PHST- 2016/11/06 06:00 [entrez] AID - jimmunol.1600103 [pii] AID - 10.4049/jimmunol.1600103 [doi] PST - ppublish SO - J Immunol. 2016 Dec 1;197(11):4312-4324. doi: 10.4049/jimmunol.1600103. Epub 2016 Nov 4.