Beyond toxicity: aryl hydrocarbon receptor-mediated functions in the immune system - PubMed (original) (raw)
Beyond toxicity: aryl hydrocarbon receptor-mediated functions in the immune system
Brigitta Stockinger. J Biol. 2009.
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.
Figures
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.
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References
- Fernandez-Salguero PM, Ward JM, Sundberg JP, Gonzalez FJ. Lesions of aryl-hydrocarbon receptor-deficient mice. Vet Pathol. 1997;34:605–614. - PubMed
- Mimura J, Yamashita K, Nakamura K, Morita M, Takagi TN, Nakao K, Ema M, Sogawa K, Yasuda M, Katsuki M, Fujii-Kuriyama Y. Loss of teratogenic response to 2,3,7,8-tetra-chlorodibenzo-p-dioxin (TCDD) in mice lacking the Ah (dioxin) receptor. Genes Cells. 1997;2:645–654. doi: 10.1046/j.1365-2443.1997.1490345.x. - DOI - PubMed
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