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Beyond toxicity: aryl hydrocarbon receptor-mediated functions in the immune system.

Stockinger B - J. Biol. (2009)

Bottom Line: The aryl hydrocarbon receptor is a ligand-activated transcriptional regulator that binds dioxin and other exogenous contaminants and is responsible for their toxic effects, including immunosuppression.New evidence suggests, however, that the aryl hydrocarbon receptor has a physiological role in the immune system, and the immunosuppressive effects of dioxin may reflect a more subtle disruption of the regulatory interactions between immune cells.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of Molecular Immunology, MRC National Institute for Medical Research, Mill Hill, London NW7 1AA, UK. bstocki@nimr.mrc.ac.uk

ABSTRACT
The aryl hydrocarbon receptor is a ligand-activated transcriptional regulator that binds dioxin and other exogenous contaminants and is responsible for their toxic effects, including immunosuppression. New evidence suggests, however, that the aryl hydrocarbon receptor has a physiological role in the immune system, and the immunosuppressive effects of dioxin may reflect a more subtle disruption of the regulatory interactions between immune cells.

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Related in: MedlinePlus

Functional subsets of CD4 T cells. Naïve CD4 T cells – that is, T cells that have not yet been activated by antigen – circulate in the blood and lymph until they are activated, usually by dendritic cells, which are specialized for that function. They then proliferate and differentiate into different functional subsets, distinguished by the different cytokines they produce (indicated under each CD4 T cell type): the cytokines act on other immune cells, activating them in turn. The four known subsets of CD4 T cells are TH1 cells, which induce infl ammatory responses that protect the tissues; TH2 cells, which are largely responsible for protecting the epithelial surfaces of the gut, lung and genitourinary system; TH17 cells, which produce early infl ammatory responses; and TREG cells, which inhibit the responses of the other cell types and are thought to provide protection from autoimmune disease. IFN, interferon; IL, interleukin, NK, natural killer; TGF, transforming growth factor. Modifi ed from Figure 5–22 in DeFranco AL, Locksley RM, Robertson M: Immunity: The Immune Response in Infectious and Infl ammatory Disease. London: New Science Press; 2007.
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Figure 1: Functional subsets of CD4 T cells. Naïve CD4 T cells – that is, T cells that have not yet been activated by antigen – circulate in the blood and lymph until they are activated, usually by dendritic cells, which are specialized for that function. They then proliferate and differentiate into different functional subsets, distinguished by the different cytokines they produce (indicated under each CD4 T cell type): the cytokines act on other immune cells, activating them in turn. The four known subsets of CD4 T cells are TH1 cells, which induce infl ammatory responses that protect the tissues; TH2 cells, which are largely responsible for protecting the epithelial surfaces of the gut, lung and genitourinary system; TH17 cells, which produce early infl ammatory responses; and TREG cells, which inhibit the responses of the other cell types and are thought to provide protection from autoimmune disease. IFN, interferon; IL, interleukin, NK, natural killer; TGF, transforming growth factor. Modifi ed from Figure 5–22 in DeFranco AL, Locksley RM, Robertson M: Immunity: The Immune Response in Infectious and Infl ammatory Disease. London: New Science Press; 2007.

Mentions: The lymphocytes of the adaptive immune system fall into two major classes – B cells, which secrete antibodies, and T cells, which act on other cells and, broadly speaking, either activate other cells of the immune system (cells that do this belong to a class known as CD4 T cells, or T helper cells) or destroy infected cells (most cells that do this belong to a class known as CD8 T cells). CD4 T cells are further subdivided into four clearly defined subsets with distinct functions that are mediated by the distinct cytokines they secrete and that act on other immune cells (Figure 1), including B cells, which they activate to secrete antibody. All CD4 T cells to some extent regulate one another's activation, but regulatory T cells (TREG cells) are specialized for suppressing the other subsets and are thought to be essential for preventing autoimmunity. Clearly, disruption of these regulatory interactions is likely to have complex effects.


Beyond toxicity: aryl hydrocarbon receptor-mediated functions in the immune system.

Stockinger B - J. Biol. (2009)

Functional subsets of CD4 T cells. Naïve CD4 T cells – that is, T cells that have not yet been activated by antigen – circulate in the blood and lymph until they are activated, usually by dendritic cells, which are specialized for that function. They then proliferate and differentiate into different functional subsets, distinguished by the different cytokines they produce (indicated under each CD4 T cell type): the cytokines act on other immune cells, activating them in turn. The four known subsets of CD4 T cells are TH1 cells, which induce infl ammatory responses that protect the tissues; TH2 cells, which are largely responsible for protecting the epithelial surfaces of the gut, lung and genitourinary system; TH17 cells, which produce early infl ammatory responses; and TREG cells, which inhibit the responses of the other cell types and are thought to provide protection from autoimmune disease. IFN, interferon; IL, interleukin, NK, natural killer; TGF, transforming growth factor. Modifi ed from Figure 5–22 in DeFranco AL, Locksley RM, Robertson M: Immunity: The Immune Response in Infectious and Infl ammatory Disease. London: New Science Press; 2007.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2736674&req=5

Figure 1: Functional subsets of CD4 T cells. Naïve CD4 T cells – that is, T cells that have not yet been activated by antigen – circulate in the blood and lymph until they are activated, usually by dendritic cells, which are specialized for that function. They then proliferate and differentiate into different functional subsets, distinguished by the different cytokines they produce (indicated under each CD4 T cell type): the cytokines act on other immune cells, activating them in turn. The four known subsets of CD4 T cells are TH1 cells, which induce infl ammatory responses that protect the tissues; TH2 cells, which are largely responsible for protecting the epithelial surfaces of the gut, lung and genitourinary system; TH17 cells, which produce early infl ammatory responses; and TREG cells, which inhibit the responses of the other cell types and are thought to provide protection from autoimmune disease. IFN, interferon; IL, interleukin, NK, natural killer; TGF, transforming growth factor. Modifi ed from Figure 5–22 in DeFranco AL, Locksley RM, Robertson M: Immunity: The Immune Response in Infectious and Infl ammatory Disease. London: New Science Press; 2007.
Mentions: The lymphocytes of the adaptive immune system fall into two major classes – B cells, which secrete antibodies, and T cells, which act on other cells and, broadly speaking, either activate other cells of the immune system (cells that do this belong to a class known as CD4 T cells, or T helper cells) or destroy infected cells (most cells that do this belong to a class known as CD8 T cells). CD4 T cells are further subdivided into four clearly defined subsets with distinct functions that are mediated by the distinct cytokines they secrete and that act on other immune cells (Figure 1), including B cells, which they activate to secrete antibody. All CD4 T cells to some extent regulate one another's activation, but regulatory T cells (TREG cells) are specialized for suppressing the other subsets and are thought to be essential for preventing autoimmunity. Clearly, disruption of these regulatory interactions is likely to have complex effects.

Bottom Line: The aryl hydrocarbon receptor is a ligand-activated transcriptional regulator that binds dioxin and other exogenous contaminants and is responsible for their toxic effects, including immunosuppression.New evidence suggests, however, that the aryl hydrocarbon receptor has a physiological role in the immune system, and the immunosuppressive effects of dioxin may reflect a more subtle disruption of the regulatory interactions between immune cells.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of Molecular Immunology, MRC National Institute for Medical Research, Mill Hill, London NW7 1AA, UK. bstocki@nimr.mrc.ac.uk

ABSTRACT
The aryl hydrocarbon receptor is a ligand-activated transcriptional regulator that binds dioxin and other exogenous contaminants and is responsible for their toxic effects, including immunosuppression. New evidence suggests, however, that the aryl hydrocarbon receptor has a physiological role in the immune system, and the immunosuppressive effects of dioxin may reflect a more subtle disruption of the regulatory interactions between immune cells.

Show MeSH
Related in: MedlinePlus