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

由于多聚唾液酸水平降低,GATA1 缺陷的树突状细胞表现出 CCL21 依赖性向淋巴结迁移受损

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作者: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, T

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.

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