LeA(H)Rning self-control

Abstract

The aryl hydrocarbon receptor (AhR) is an important regulator of the immune response. A report by Puccetti and coworkers describes a regulatory pathway by which L-kynurenine (L-Kyn) produced by tryptophan 2,3-dioxygenase 2 (TDO2) activates AhR in cells of the innate immune system to limit endotoxin-triggered inflammation through a mechanism that involves the non-enzymatic anti-inflammatory activities of indoleamine 2,3-dioxygenase 1 (IDO1).

Figure 1

Control of endotoxin tolerance by AhR. TDO2 expression induced by LPS in a TLR4-dependent manner results in the production of L-Kyn and the activation of AhR in cells of the innate immune system. AhR activation induces IDO1 expression through its genomic signaling pathway, and also triggers IDO1 phosphorylation as a result of c-SRC activation through its non-genomic signaling pathway, resulting in the establishment of endotoxin tolerance.