Differential Influences of the Aryl Hydrocarbon Receptor on Th17 Mediated Responses <i>in vitro</i> and <i>in vivo</i>

<div><p>The aryl hydrocarbon receptor (AhR) has been attributed with anti-inflammatory effects in the development of pathological immune responses leading to experimental autoimmune encephalomyelitis (EAE) via the induction of regulatory T cells. In agreement with previously published findings, we find that TCDD administration confers protection from EAE, however, this immuno-modulatory effect was not the consequence of <i>de novo</i> Treg generation, but the inhibition of Th17 cell differentiation. Systemic application of FICZ at the time of immunization also reduced EAE pathology albeit to a lesser degree than TCDD. <i>In vitro</i> Th17 differentiation in the presence of AhR agonists, including TCDD, promoted IL-17 and IL-22 expression, but did not induce Treg differentiation. AhR affinity influenced the amounts of IL-17 and IL-22 protein that was secreted by Th17 cells, but did not seem to affect susceptibility to EAE <i>in vivo</i>. Making use of conditional AhR-deficient mice, we show that the anti-inflammatory effect of TCDD depends on AhR activation in both T cells and dendritic cells, further emphasising the ability of TCDD to interfere with T effector cell differentiation <i>in vivo</i>. The dichotomy between the <i>in vivo</i> and <i>in vitro</i> effects of AhR reveals the complexity of the AhR pathway, which has the capacity of affecting different AhR-expressing cell types involved in mounting immune responses, thus participating in defining their outcome.</p>