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The aryl hydrocarbon receptor (AHR) is a ligand-dependent member of the PAS-bHLHfamily of nuclear receptors. Anthropogenic ligands include environmental contaminants such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Over-activation of the AHR causes thymus atrophy and immunosuppression. Signaling via the AHR changes the thymocyte differentiation program at several checkpoints, in particular within the CD4 -CD8 -double-negative (DN) thymocyte subset. Here, we show that AHR overactivation led to the preferential emigration of DN thymocytes to the periphery and accumulation in the spleen. Some of these recent thymic emigrants (RTE) had a novel "activated immature" phenotype (CD3 -TCRb -CD25 +/int CD44 -CD45RB +/int CD62L + -CD69 -cells). Gene expression profiling of DN RTE revealed 15 genes that were upregulated more than threefold by TCDD, including the S100A9 gene. Exposure of S100A9 null mice to TCDD showed a role for this protein in AHR-mediated thymic egress.

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