Aryl hydrocarbon receptor signaling mediates expression of indoleamine 2,3-dioxygenase

Biochem Biophys Res Commun. 2008 Oct 24;375(3):331-5. doi: 10.1016/j.bbrc.2008.07.156. Epub 2008 Aug 9.


Aryl hydrocarbon receptor (AhR) activation by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) leads to immune suppression associated with the induction of regulatory T cells (T(reg)) expressing the transcription factor Foxp3. The immunological mechanisms of suppression are not well understood however dendritic cells (DC) are considered a key target for AhR-mediated immune suppression. Here we show that activation of AhR by TCDD induces DC indoleamine 2,3-dioxygenase 1 (IDO1) and indoleamine 2,3-dioxygenase-like protein (IDO2). Induction of IDO1 and IDO2 was also found in lung and spleen associated with an increase of the T(reg) marker Foxp3 in spleen of TCDD-treated C57BL/6 mice, which is suppressed by inhibition of IDO. These data indicate that AhR-activation is an important signaling pathway for IDO expression and suggest a critical role of IDO in the mechanism leading to the generation of T(reg) that mediates the immune suppression through activation of AhR.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Immune Tolerance*
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / metabolism*
  • Interferon-gamma / pharmacology
  • Mice
  • Mice, Inbred C57BL
  • Polychlorinated Dibenzodioxins / pharmacology
  • Receptors, Aryl Hydrocarbon / agonists
  • Receptors, Aryl Hydrocarbon / metabolism*
  • Signal Transduction
  • T-Lymphocytes, Regulatory / drug effects
  • T-Lymphocytes, Regulatory / enzymology
  • T-Lymphocytes, Regulatory / immunology*


  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • Polychlorinated Dibenzodioxins
  • Receptors, Aryl Hydrocarbon
  • Interferon-gamma