Role of the aryl hydrocarbon receptor in thymocyte emigration in vivo.
The aryl hydrocarbon receptor (AHR) is a ligand-dependent member of the PAS-bHLH-family 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 over-activation 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-TCRbeta-CD25+/intCD44-CD45RB+/intCD62L+CD69- cells). Gene expression profiling of DN RTE revealed 15 genes that were up-regulated 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.
Temchura
Vladimir V
VV
Institute for Environmental Medical Research (IUF), Heinrich-Heine University of Düsseldorf, Düsseldorf, Germany.
Frericks
Markus
M
Nacken
Wolfgang
W
Esser
Charlotte
C
D000818:Animals; D040502:Calgranulin B / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology*; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D016130:Immunophenotyping; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology; D012313:RNA / Q000737:chemistry / Q000235:genetics; D018336:Receptors, Aryl Hydrocarbon / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
D040502:Calgranulin B; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D012313:RNA