Aryl Hydrocarbon Receptor Controls Monocyte Differentiation into Dendritic Cells versus Macrophages

Immunity. 2017 Sep 19;47(3):582-596.e6. doi: 10.1016/j.immuni.2017.08.016.


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.

Keywords: IRF4; MAFB; aryl hydrocarbon receptor; dendritic cell; human; macrophage; monocyte.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Ascites
  • Cells, Cultured
  • Cluster Analysis
  • Cytokines / metabolism
  • Cytokines / pharmacology
  • Dendritic Cells / cytology
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism*
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Humans
  • Interferon Regulatory Factors / metabolism
  • Leprosy / immunology
  • Leprosy / metabolism
  • Leprosy / microbiology
  • Macrophages / cytology
  • Macrophages / drug effects
  • Macrophages / immunology
  • Macrophages / metabolism*
  • MafB Transcription Factor / metabolism
  • Male
  • Mice
  • Mice, Knockout
  • Monocytes / cytology
  • Monocytes / drug effects
  • Monocytes / immunology
  • Monocytes / metabolism*
  • Neoplasms / genetics
  • Neoplasms / metabolism
  • Positive Regulatory Domain I-Binding Factor 1
  • Receptors, Aryl Hydrocarbon / genetics
  • Receptors, Aryl Hydrocarbon / metabolism*
  • Repressor Proteins / metabolism
  • Transcriptome


  • Cytokines
  • Interferon Regulatory Factors
  • MafB Transcription Factor
  • Receptors, Aryl Hydrocarbon
  • Repressor Proteins
  • interferon regulatory factor-4
  • PRDM1 protein, human
  • Positive Regulatory Domain I-Binding Factor 1