title: Constitutively active aryl hydrocarbon receptor expressed in T cells increases immunization-induced IFN-gamma production in mice but does not suppress T(h)2-cytokine production or antibody production.
abstract: 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-gamma production in the spleen and suppresses the production of T(h)2 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-gamma production upon OVA immunization. By contrast, production of T(h)2 cytokines and antibodies were not significantly suppressed by CA-AhR in the T cells. These results suggest that suppression of T(h)2 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-gamma augmentation and T(h)2 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 T(h)2 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.
authors.affiliation: Environmental Health Sciences Division, National Institute for Environmental Studies, Tsukuba, Japan. keikon@nies.go.jp
authors.forename: Keiko
authors.initials: K
authors.lastname: Nohara
authors.forename: Takehiro
authors.initials: T
authors.lastname: Suzuki
authors.forename: Kana
authors.initials: K
authors.lastname: Ao
authors.forename: Hikari
authors.initials: H
authors.lastname: Murai
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Miyamoto
authors.forename: Kaoru
authors.initials: K
authors.lastname: Inouye
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Pan
authors.forename: Hozumi
authors.initials: H
authors.lastname: Motohashi
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Fujii-Kuriyama
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Chiharu
authors.initials: C
authors.lastname: Tohyama
mesh_terms: D000818:Animals; D000906:Antibodies / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology; D018336:Receptors, Aryl Hydrocarbon / Q000819:agonists / Q000276:immunology*; D013154:Spleen / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D013950:Thymus Gland / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
chemical_list: D000906:Antibodies; D016207:Cytokines; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D007371:Interferon-gamma; D010047:Ovalbumin