International Immunology Advance Access originally published online on May 21, 2009
International Immunology 2009 21(7):769-777; doi:10.1093/intimm/dxp045
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Constitutively active aryl hydrocarbon receptor expressed in T cells increases immunization-induced IFN-
production in mice but does not suppress Th2-cytokine production or antibody production
1 Environmental Health Sciences Division, National Institute for Environmental Studies, Tsukuba 305-8506, Japan
2 Tohoku Universtiy Graduate School of Medicine, Sendai 980-8575, Japan
3 Center for Tsukuba Advanced Research Alliance, University of Tsukuba, Tsukuba 305-8575, Japan
4 Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, University of Tokyo, Tokyo 113-0033, Japan
Correspondence to: K. Nohara; Environmental Health Sciences Division, National Institute for Environmental Studies, Tsukuba 305-8506, Japan; E-mail: keikon{at}nies.go.jp
The ligand-dependent transcription factor aryl hydrocarbon receptor (AhR) has been implicated in various immune functions. Our previous studies have shown that AhR activation by exposure of ovalbumin (OVA)-immunized mice to the potent ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) increases immunization-induced IFN-
production in the spleen and suppresses the production of Th2 cytokines and OVA-specific antibodies. In the present study, we used transgenic (Tg) mice that express a constitutively active mutant of aryl hydrocarbon receptor (CA-AhR) specifically in T-lineage cells to clarify the role of AhR activation in T cells in these reactions. The results of this study clearly demonstrated that AhR activation only in the T cells augments IFN- production upon OVA immunization. By contrast, production of Th2 cytokines and antibodies were not significantly suppressed by CA-AhR in the T cells. These results suggest that suppression of Th2 cytokines and antibodies production require AhR activation not only in T cells but also in other cell types as caused by TCDD exposure. Alternatively, these results may indicate that IFN- augmentation and Th2 cytokines and antibodies suppression depend on different ways of functions of AhR in the T cells and that CA-AhR does not replicate the suppressive effect of TCDD-activated AhR on Th2 cytokines and antibodies. Expression of CA-AhR in the T cells was also shown to increase the percentage of CD25+ cells among CD4+ cells in the thymus and spleen. Thus, studies using T-cell-specific CA-AhR Tg mice provide a way to dissect the role of AhR in individual cell types and how the AhR functions.
Keywords: AhR, TCDD, transcription factor, transgenic mice
Transmitting editor: T. Saito
Received 9 November 2008, accepted 20 April 2009.