Aryl Hydrocarbon Receptor Controls Monocyte Differentiation into Dendritic Cells versus Macrophages

Christel L Goudot (1) , Alice Coillard (1) , Alexandra-Chloé Villani (2) , Paul Gueguen (1) , Adeline Cros (1) , Siranush Sarkizova , Tsing-Lee Tang-Huau (3) , Mylène Bohec (4) , Sylvain Baulande (5) , Nir Hacohen (6) , Sebastian Amigorena (1) , Elodie Segura (1)

1 U932 - Immunité et cancer
2 BROAD INSTITUTE - Broad Institute of MIT and Harvard
3 Sanofi [Vitry-sur-Seine]
4 PSL - Université Paris Sciences et Lettres
5 Institut Curie [Paris]
6 Massachusetts General Hospital [Boston]

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.

Domaines: Immunité adaptative; Immunité innée

Christel L Goudot, Alice Coillard, Alexandra-Chloé Villani, Paul Gueguen, Adeline Cros, et al.. Aryl Hydrocarbon Receptor Controls Monocyte Differentiation into Dendritic Cells versus Macrophages. Immunity, 2017, 47 (3), pp.582 - 596.e6. ⟨10.1016/j.immuni.2017.08.016⟩. ⟨hal-01613828⟩