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

MR Scheenstra; IM De Cuyper; F Branco-Madeira; P de Bleser; M Kool; M Meinders; M Hoogenboezem; E Mu; MC Wolkers; F Salerno; B Nota; Y Saeys; S Klarenbeek; Wilfred van Ijcken; H Hammad; Sjaak Philipsen; TK van den Berg; TW Kuijpers; Bart Lambrecht; L Gutierrez

doi:10.4049/jimmunol.1600103

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

MR Scheenstra, IM De Cuyper, F Branco-Madeira, P de Bleser, M Kool, M Meinders, M Hoogenboezem, E Mu, MC Wolkers, F Salerno, B Nota, Y Saeys, S Klarenbeek, Wilfred van Ijcken, H Hammad, Sjaak Philipsen, TK van den Berg, TW Kuijpers, Bart Lambrecht, L Gutierrez

Research output: Contribution to journal › Article › Academic › peer-review

11 Citations (Scopus)

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

Original language	English
Pages (from-to)	4312-4324
Number of pages	13
Journal	Journal of Immunology
Volume	197
Issue number	11
DOIs	https://doi.org/10.4049/jimmunol.1600103
Publication status	Published - 2016

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10.4049/jimmunol.1600103

http://hdl.handle.net/1765/94418

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Scheenstra, MR., De Cuyper, IM., Branco-Madeira, F., de Bleser, P., Kool, M., Meinders, M., Hoogenboezem, M., Mu, E., Wolkers, MC., Salerno, F., Nota, B., Saeys, Y., Klarenbeek, S., van Ijcken, W., Hammad, H., Philipsen, S., van den Berg, TK., Kuijpers, TW., Lambrecht, B., & Gutierrez, L. (2016). GATA1-Deficient Dendritic Cells Display Impaired CCL21-Dependent Migration toward Lymph Nodes Due to Reduced Levels of Polysialic Acid. Journal of Immunology, 197(11), 4312-4324. https://doi.org/10.4049/jimmunol.1600103

@article{c36f3124fa8b4eb583176f7d9fc5171d,

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

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

author = "MR Scheenstra and {De Cuyper}, IM and F Branco-Madeira and {de Bleser}, P and M Kool and M Meinders and M Hoogenboezem and E Mu and MC Wolkers and F Salerno and B Nota and Y Saeys and S Klarenbeek and {van Ijcken}, Wilfred and H Hammad and Sjaak Philipsen and {van den Berg}, TK and TW Kuijpers and Bart Lambrecht and L Gutierrez",

year = "2016",

doi = "10.4049/jimmunol.1600103",

language = "English",

volume = "197",

pages = "4312--4324",

journal = "Journal of Immunology",

issn = "0022-1767",

publisher = "American Association of Immunologists",

number = "11",

}

Scheenstra, MR, De Cuyper, IM, Branco-Madeira, F, de Bleser, P, Kool, M, Meinders, M, Hoogenboezem, M, Mu, E, Wolkers, MC, Salerno, F, Nota, B, Saeys, Y, Klarenbeek, S, van Ijcken, W, Hammad, H, Philipsen, S, van den Berg, TK, Kuijpers, TW, Lambrecht, B & Gutierrez, L 2016, 'GATA1-Deficient Dendritic Cells Display Impaired CCL21-Dependent Migration toward Lymph Nodes Due to Reduced Levels of Polysialic Acid', Journal of Immunology, vol. 197, no. 11, pp. 4312-4324. https://doi.org/10.4049/jimmunol.1600103

TY - JOUR

T1 - GATA1-Deficient Dendritic Cells Display Impaired CCL21-Dependent Migration toward Lymph Nodes Due to Reduced Levels of Polysialic Acid

AU - Scheenstra, MR

AU - De Cuyper, IM

AU - Branco-Madeira, F

AU - de Bleser, P

AU - Kool, M

AU - Meinders, M

AU - Hoogenboezem, M

AU - Mu, E

AU - Wolkers, MC

AU - Salerno, F

AU - Nota, B

AU - Saeys, Y

AU - Klarenbeek, S

AU - van Ijcken, Wilfred

AU - Hammad, H

AU - Philipsen, Sjaak

AU - van den Berg, TK

AU - Kuijpers, TW

AU - Lambrecht, Bart

AU - Gutierrez, L

PY - 2016

Y1 - 2016

N2 - 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 Gatal knockout mice (Gatal-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 Gatal-KODc mice. Migration assays performed in vitro showed that this defect was selective for CCL21, but not CCL19. Interestingly, we show that Gatal-KODc DCs have reduced polysialic acid levels on their surface, which is a known determinant for the proper migration of DCs toward CCL21.

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

U2 - 10.4049/jimmunol.1600103

DO - 10.4049/jimmunol.1600103

M3 - Article

VL - 197

SP - 4312

EP - 4324

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 11

ER -

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

Abstract

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