tetano
Editor, Senior Moderator
Eur J Immunol. 2014 Feb 12. doi: 10.1002/eji.201343980. [Epub ahead of print]
New insights into the role of the aryl hydrocarbon receptor in the function of CD11c+ cells during respiratory viral infection.
Jin GB, Winans B, Martin KC, Lawrence BP.
Author information
Abstract
The aryl hydrocarbon receptor (AHR) has garnered considerable attention as a modulator of CD4 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 MLNs, and decreases their frequency in the lung. DNA binding domain (DBD) Ahr mutants demonstrate that alterations in DC subsets require the ligand-activated AHR to contain its inherent DBD. To evaluate the intrinsic role of AHR in DCs, conditional knockouts were created using Cre-LoxP technology, which reveal 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 na?ve CD8+ T-cell activation in the draining lymphoid nodes. These findings indicate DCs are among 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. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
KEYWORDS:
Antiviral immunity, CD8+ T cells, Dendritic cells (DCs), Influenza A virus
PMID:
24519489
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24519489
New insights into the role of the aryl hydrocarbon receptor in the function of CD11c+ cells during respiratory viral infection.
Jin GB, Winans B, Martin KC, Lawrence BP.
Author information
Abstract
The aryl hydrocarbon receptor (AHR) has garnered considerable attention as a modulator of CD4 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 MLNs, and decreases their frequency in the lung. DNA binding domain (DBD) Ahr mutants demonstrate that alterations in DC subsets require the ligand-activated AHR to contain its inherent DBD. To evaluate the intrinsic role of AHR in DCs, conditional knockouts were created using Cre-LoxP technology, which reveal 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 na?ve CD8+ T-cell activation in the draining lymphoid nodes. These findings indicate DCs are among 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. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
KEYWORDS:
Antiviral immunity, CD8+ T cells, Dendritic cells (DCs), Influenza A virus
PMID:
24519489
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24519489