Comparative transcriptional and functional profiling defines conserved programs of intestinal DC differentiation in humans and mice

Payal B. Watchmaker, Katharina Lahl, Mike Lee, Dirk Baumjohann, John Morton, Sun Jung Kim, Ruizhu Zeng, Alexander Dent, K. Mark Ansel, Betty Diamond, Husein Hadeiba, Eugene C. Butcher

Research output: Contribution to journalArticle

142 Scopus citations

Abstract

Dendritic cells (DCs) that orchestrate mucosal immunity have been studied in mice. Here we characterized human gut DC populations and defined their relationship to previously studied human and mouse DCs. CD103 +Sirpα- DCs were related to human blood CD141 + DCs 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 the induction of regulatory T cells. Both CD103+ DC subsets induced the T H17 subset of helper T cells, while CD103 -Sirpα+ DCs induced the TH1 subset of helper T cells. Comparative analysis of transcriptomes revealed conserved transcriptional programs among CD103+ DC subsets and identified a selective role for the transcriptional repressors Bcl-6 and Blimp-1 in the specification of CD103+CD11b- DCs and intestinal CD103+CD11b+ DCs, respectively. Our results highlight evolutionarily conserved and divergent programming of intestinal DCs.

Original languageEnglish (US)
Pages (from-to)98-108
Number of pages11
JournalNature Immunology
Volume15
Issue number1
DOIs
StatePublished - Jan 2014

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Watchmaker, P. B., Lahl, K., Lee, M., Baumjohann, D., Morton, J., Kim, S. J., Zeng, R., Dent, A., Ansel, K. M., Diamond, B., Hadeiba, H., & Butcher, E. C. (2014). Comparative transcriptional and functional profiling defines conserved programs of intestinal DC differentiation in humans and mice. Nature Immunology, 15(1), 98-108. https://doi.org/10.1038/ni.2768