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

Authors: Jin, Guang-Bi; Winans, Bethany; Martin, Kyle C; Paige Lawrence, B

Published In Eur J Immunol, (2014 Jun)

Abstract: 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.

PubMed ID: 24519489 Exiting the NIEHS site

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

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