Loss of Bcl6 transcriptionally alters classical dendritic cells and diminishes T follicular helper cell and Th17-inducing cDC2 in mice

Abstract

ABSTRACTConventional dendritic cells (cDC) play key roles in immune induction, but what drives their heterogeneity and functional specialization is still ill-defined. Here we show that deletion of the transcriptional repressor Bcl6 in murine cDC alters the phenotype and transcriptome of cDC1 and cDC2, while their lineage identity is preserved. Bcl6-deficient cDC1 were diminished in the periphery but maintained their ability to cross-present antigen to CD8+T cells, confirming general maintenance of this subset. Surprisingly, the absence of Bcl6 in cDC caused a complete loss of Notch2-dependent cDC2 in the spleen and intestinal lamina propria. DC-targeted Bcl6-deficient mice induced fewer T follicular helper cells in response to the model antigen ovalbumin and mounted diminished Th17 immunity toCitrobacter rodentiumin the colon. Our findings establish Bcl6 as an essential transcription factor for subsets of cDC and add to our understanding of the transcriptional landscape underlying cDC heterogeneity.