Transcriptional and functional profiling of human intestinal dendritic cells reveals conserved specialization and a role for Bcl-6 and Blimp-1 in terminal subset differentiation

Dendritic cells (DCs) that orchestrate mucosal immunity have been studied in mice. Here we characterize human gut DC populations, and define their relationship to previously studied human and mouse DCs. CD103(+)Sirpα(−) DCs were related to human blood CD141(+) and to mouse intestinal CD103(+)CD11b(−) DCs and expressed markers of cross-presenting DCs. CD103(+)Sirpα(+) DCs aligned with human blood CD1c(+) DCs and mouse intestinal CD103(+)CD11b(+) DCs and supported regulatory T cell induction. Both CD103(+) DC subsets induced T(H)17 cells, while CD103(−)Sirpα(+) DCs induced T(H)1 cells. Comparative transcriptomics revealed conserved transcriptional programs among CD103(+) DC subsets and uncovered a selective role for Bcl-6 and Blimp-1 in CD103(+)Sirpα(−) and intestinal CD103(+)CD11b(+) DC specification, respectively. These results highlight evolutionarily conserved and divergent programming of intestinal DCs.