title: New insights into the role of the aryl hydrocarbon receptor in the function of CD11c⁺ cells during respiratory viral infection.
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.
authors: Department of Environmental Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.
authors: Guang-Bi
authors: GB
authors: Jin
authors: Department of Environmental Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.
authors: Bethany
authors: B
authors: Winans
authors: Department of Environmental Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.
authors: Kyle C
authors: KC
authors: Martin
authors: Department of Environmental Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.|Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.
authors: B
authors: B
authors: Paige Lawrence
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D039481:CD11b Antigen / Q000235:genetics / Q000276:immunology; D039521:CD11c Antigen / Q000235:genetics / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D003713:Dendritic Cells / Q000378:metabolism* / Q000473:pathology; D009980:Influenza A virus / Q000276:immunology*; D039001:Integrin alpha Chains / Q000235:genetics / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009976:Orthomyxoviridae Infections / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics / Q000276:immunology*; D012141:Respiratory Tract Infections / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology
chemical_list: D015703:Antigens, CD; D039481:CD11b Antigen; D039521:CD11c Antigen; D039001:Integrin alpha Chains; D018336:Receptors, Aryl Hydrocarbon; C091367:alpha E integrins
keywords: Antiviral immunity; CD8+ T cells; Dendritic cells (DCs); Influenza A virus