Aryl Hydrocarbon Receptor Controls Monocyte Differentiation into Dendritic Cells versus Macrophages.
Christel Goudot, Alice Coillard, Alexandra-Chloé Villani, Paul Gueguen, Adeline Cros, Siranush Sarkizova, Tsing-Lee Tang-Huau, Mylène Bohec, Sylvain Baulande, Nir Hacohen, Sebastian Amigorena, Elodie Segura
Author Information
Christel Goudot: Institut Curie, PSL Research University, INSERM, U932, 26 rue d'Ulm, 75005 Paris, France.
Alice Coillard: Institut Curie, PSL Research University, INSERM, U932, 26 rue d'Ulm, 75005 Paris, France.
Alexandra-Chloé Villani: Broad Institute of Harvard University and MIT, Cambridge, MA 02142, USA; Center for Cancer Research, Massachusetts General Hospital, Department of Medicine, Charlestown, MA 02129, USA.
Paul Gueguen: Institut Curie, PSL Research University, INSERM, U932, 26 rue d'Ulm, 75005 Paris, France.
Adeline Cros: Institut Curie, PSL Research University, INSERM, U932, 26 rue d'Ulm, 75005 Paris, France.
Siranush Sarkizova: Department of Biomedical Informatics, Harvard Medical School, Boston, MA 02142, USA.
Tsing-Lee Tang-Huau: Institut Curie, PSL Research University, INSERM, U932, 26 rue d'Ulm, 75005 Paris, France; Sanofi, Breakthrough Laboratory, 1 impasse des ateliers, 94400 Vitry-sur-Seine, France.
Mylène Bohec: Institut Curie, PSL Research University, NGS platform, 26 rue d'Ulm, 75005 Paris, France.
Sylvain Baulande: Institut Curie, PSL Research University, NGS platform, 26 rue d'Ulm, 75005 Paris, France.
Nir Hacohen: Broad Institute of Harvard University and MIT, Cambridge, MA 02142, USA; Center for Cancer Research, Massachusetts General Hospital, Department of Medicine, Charlestown, MA 02129, USA.
Sebastian Amigorena: Institut Curie, PSL Research University, INSERM, U932, 26 rue d'Ulm, 75005 Paris, France.
Elodie Segura: Institut Curie, PSL Research University, INSERM, U932, 26 rue d'Ulm, 75005 Paris, France. Electronic address: elodie.segura@curie.fr.
After entering tissues, monocytes differentiate into cells that share functional features with either macrophages or dendritic cells (DCs). How monocyte fate is directed toward monocyte-derived macrophages (mo-Macs) or monocyte-derived DCs (mo-DCs) and which transcription factors control these differentiation pathways remains unknown. Using an in vitro culture model yielding human mo-DCs and mo-Macs closely resembling those found in vivo in ascites, we show that IRF4 and MAFB were critical regulators of monocyte differentiation into mo-DCs and mo-Macs, respectively. Activation of the aryl hydrocarbon receptor (AHR) promoted mo-DC differentiation through the induction of BLIMP-1, while impairing differentiation into mo-Macs. AhR deficiency also impaired the in vivo differentiation of mouse mo-DCs. Finally, AHR activation correlated with mo-DC infiltration in leprosy lesions. These results establish that mo-DCs and mo-Macs are controlled by distinct transcription factors and show that AHR acts as a molecular switch for monocyte fate specification in response to micro-environmental factors.
