Impact of the Type I Interferon Receptor on the Global Gene Expression Program During the Course of Dendritic Cell Maturation Induced by Polyinosinic Polycytidylic Acid

Abstract

Dendritic cell (DC) maturation involves widespread changes in cellular function and gene expression. The regulatory role of IFNAR in the program of DC maturation remains incompletely defined. Thus, the time evolution impact of IFNAR on this process was evaluated. Changes in DC phenotype, function, and gene expression induced by poly I:C were measured in wild-type and IFNAR(-/-) DC at 9 time points over 24 h. Temporal gene expression profiles were filtered on consistency and response magnitude across replicates. The number of genes whose expression was altered by poly I:C treatment was greatly reduced in IFNAR(-/-) DC, including the majority of the downregulated gene expression program previously observed in wild-type (WT) DC. Furthermore, the number of genes upregulated was almost equal between WT and IFNAR(-/-) DC, yet the identities of those genes were distinct. Integrating these data with protein-protein interaction data revealed several novel subnetworks active during maturation, including nucleotide synthesis, metabolism, and repair. A subnetwork associated with redox activity was uniquely identified in IFNAR(-/-) DC. Overall, temporal gene expression and network analyses identified many genes regulated by the type I interferon response and revealed previously unidentified aspects of the DC maturation process.