GATA1-deficient dendritic cells display impaired CCL21-dependent migration towards 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 suggests 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-Seq analysis revealed a number of deregulated genes involved in cell survival, migration and function. DC migration towards 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 towards CCL21. Overall design: Dendritic cells from Gata1 knock-out or wild-type mice were stimulated with LPS of unstimulated (under steady state), 2 biological replicates each

8

Scheenstra MR, De Cuyper IM, Branco-Madeira F, de Bleser P, Kool M, Meinders M, Hoogenboezem M, Mul E, Wolkers MC, Salerno F, Nota B, Saeys Y, Klarenbeek S, van IJcken WF, Hammad H, Philipsen S, van den Berg TK, Kuijpers TW, Lambrecht BN, Gutiérrez L