Novel insights into the relationships between dendritic cell subsets in human and mouse revealed by genome-wide expression profiling

Scott H Robbins¹^,2^,3^,10 , Thierry Walzer¹^,2^,3 , Doulaye Dembélé⁴^,5^,6^,7 , Christelle Thibault⁴^,5^,6^,7 , Axel Defays¹^,2^,3 , Gilles Bessou¹^,2^,3 , Huichun Xu⁸ , Eric Vivier¹^,2^,3^,9 , MacLean Sellars⁴^,5^,6^,7 , Philippe Pierre¹^,2^,3 , Franck R Sharp⁸ , Susan Chan⁴^,5^,6^,7 , Philippe Kastner⁴^,5^,6^,7 and Marc Dalod¹^,2^,3

¹CIML (Centre d'Immunologie de Marseille-Luminy), Université de la Méditerranée, Parc scientifique de Luminy case 906, Marseille F-13288, France

²U631, INSERM (Institut National de la Santé et de la Recherche Médicale), Parc scientifique de Luminy case 906, Marseille F-13288, France

³UMR6102, CNRS (Centre National de la Recherche Scientifique), Parc scientifique de Luminy case 906, Marseille F-13288, France

⁴Hematopoiesis and leukemogenesis in the mouse, IGBMC (Institut de Génétique et de Biologie Moléculaire et Cellulaire), rue Laurent Fries, ILLKIRCH F-67400, France

⁵U596, INSERM, rue Laurent Fries, ILLKIRCH F-67400, France

⁶UMR7104, CNRS, rue Laurent Fries, ILLKIRCH F-67400, France

⁷UM41, Université Louis Pasteur, rue Laurent Fries, Strasbourg F-67400, France

⁸The Medical Investigation of Neurodevelopmental Disorders Institute, University of California at Davis Medical Center, Sacramento, CA 95817, USA

⁹Hôpital de la Conception, Assistance Publique-Hôpitaux de Marseille, Boulevard Baille, Marseille F-13385, France

¹⁰Current address: Genomics Institute of the Novartis Research Foundation, John Jay Hopkins Drive, San Diego, CA 92121, USA

author email corresponding author email

Genome Biology 2008, 9:R17doi:10.1186/gb-2008-9-1-r17


Published:	24 January 2008

Subject areas: Immunology, Evolution

Abstract

Background

Dendritic cells (DCs) are a complex group of cells that play a critical role in vertebrate immunity. Lymph-node resident DCs (LN-DCs) are subdivided into conventional DC (cDC) subsets (CD11b and CD8α in mouse; BDCA1 and BDCA3 in human) and plasmacytoid DCs (pDCs). It is currently unclear if these various DC populations belong to a unique hematopoietic lineage and if the subsets identified in the mouse and human systems are evolutionary homologs. To gain novel insights into these questions, we sought conserved genetic signatures for LN-DCs and in vitro derived granulocyte-macrophage colony stimulating factor (GM-CSF) DCs through the analysis of a compendium of genome-wide expression profiles of mouse or human leukocytes.

Results

We show through clustering analysis that all LN-DC subsets form a distinct branch within the leukocyte family tree, and reveal a transcriptomal signature evolutionarily conserved in all LN-DC subsets. Moreover, we identify a large gene expression program shared between mouse and human pDCs, and smaller conserved profiles shared between mouse and human LN-cDC subsets. Importantly, most of these genes have not been previously associated with DC function and many have unknown functions. Finally, we use compendium analysis to re-evaluate the classification of interferon-producing killer DCs, lin^-CD16⁺HLA-DR⁺cells and in vitro derived GM-CSF DCs, and show that these cells are more closely linked to natural killer and myeloid cells, respectively.

Conclusion

Our study provides a unique database resource for future investigation of the evolutionarily conserved molecular pathways governing the ontogeny and functions of leukocyte subsets, especially DCs.