IRF8 directly controls gene expression in APCs. The RNA-seq data were queried for hematopoietic cell–specific genes, and the density of sequence reads mapped to individual gene exons is shown for 5 controls and for K108E. (A) Neutrophil genes are enriched in K108E, and T lymphocyte genes (B) are similar in controls and patient K108E. B lymphocyte (C) and plasma cell (D) specific genes are enriched in patient K108E. (E) Transcripts expressed in APCs are depleted in K108E in agreement with published cellular immunophenotyping data of the K108E patient.⁴  The asterisk identifies genes that were found to be direct IRF8 targets in chromatin immunoprecipitation sequencing (ChIP-seq) experiments. (F) The list of genes differentially expressed in K108E was compared with a list of direct IRF8 targets (containing an IRF8 binding site within 20 kb from the transcription start site) and obtained by ChIP-seq that we recently published.²⁴  Genes bearing IRF8 binding sites are significantly enriched in the list of genes depleted in K108E, compared with genes of increased expression in K108E, or to a set of 10 randomly generated gene sets. The P value is calculated using Fisher’s exact test.