New insights into the role of the aryl hydrocarbon receptor in the function of CD11c⁺ cells during respiratory viral infection

Eur J Immunol. 2014 Jun;44(6):1685-1698. doi: 10.1002/eji.201343980. Epub 2014 Mar 19.


The aryl hydrocarbon receptor (AHR) has garnered considerable attention as a modulator of CD4(+) cell lineage development and function. It also regulates antiviral CD8(+) T-cell responses, but via indirect mechanisms that have yet to be determined. Here, we show that during acute influenza virus infection, AHR activation skews dendritic-cell (DC) subsets in the lung-draining lymph nodes, such that there are fewer conventional CD103(+) DCs and CD11b(+) DCs. Sorting DC subsets reveals AHR activation reduces immunostimulatory function of CD103(+) DCs in the mediastinal lymph nodes, and decreases their frequency in the lung. DNA-binding domain Ahr mutants demonstrate that alterations in DC subsets require the ligand-activated AHR to contain its inherent DNA-binding domain. To evaluate the intrinsic role of AHR in DCs, conditional knockouts were created using Cre-LoxP technology, which revealed that AHR in CD11c(+) cells plays a key role in controlling the acquisition of effector CD8(+) T cells in the infected lung. However, AHR within other leukocyte lineages contributes to diminished naïve CD8(+) T-cell activation in the draining lymphoid nodes. These findings indicate DCs are among the direct targets of AHR ligands in vivo, and AHR signaling modifies host responses to a common respiratory pathogen by affecting the complex interplay of multiple cell types.

Keywords: Antiviral immunity; CD8+ T cells; Dendritic cells (DCs); Influenza A virus.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antigens, CD / genetics
  • Antigens, CD / immunology
  • CD11b Antigen / genetics
  • CD11b Antigen / immunology
  • CD11c Antigen / genetics
  • CD11c Antigen / immunology*
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / pathology
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / pathology
  • Dendritic Cells / metabolism*
  • Dendritic Cells / pathology
  • Influenza A virus / immunology*
  • Integrin alpha Chains / genetics
  • Integrin alpha Chains / immunology
  • Lymph Nodes / immunology
  • Lymph Nodes / pathology
  • Mice
  • Mice, Knockout
  • Orthomyxoviridae Infections / genetics
  • Orthomyxoviridae Infections / immunology*
  • Orthomyxoviridae Infections / pathology
  • Receptors, Aryl Hydrocarbon / genetics
  • Receptors, Aryl Hydrocarbon / immunology*
  • Respiratory Tract Infections / genetics
  • Respiratory Tract Infections / immunology*
  • Respiratory Tract Infections / pathology
  • Signal Transduction / genetics
  • Signal Transduction / immunology


  • Antigens, CD
  • CD11b Antigen
  • CD11c Antigen
  • Integrin alpha Chains
  • Receptors, Aryl Hydrocarbon
  • alpha E integrins