Constitutively active aryl hydrocarbon receptor expressed specifically in T-lineage cells causes thymus involution and suppresses the immunization-induced increase in splenocytes
| Autor: | Keiko Nohara, Yoshiaki Fujii-Kuriyama, Azumi Hida, Xiaoqing Pan, Hozumi Motohashi, Shin-ichi Tsukumo, Haruko Nagai, Chiharu Tohyama, Kaoru Inouye, Masayuki Yamamoto, Tomohiro Ito |
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| Rok vydání: | 2005 |
| Předmět: |
Cell type
medicine.medical_specialty Stromal cell Polychlorinated Dibenzodioxins Immunology Down-Regulation Epitopes T-Lymphocyte Mice Transgenic Thymus Gland Mice T-Lymphocyte Subsets Internal medicine medicine Suppressor Factors Immunologic Immunology and Allergy Cytotoxic T cell Animals Humans Cell Lineage IL-2 receptor Lymphocyte Count RNA Messenger Receptor biology Organ Size respiratory system Aryl hydrocarbon receptor Molecular biology Up-Regulation Mice Inbred C57BL Thymocyte Endocrinology Receptors Aryl Hydrocarbon Mice Inbred DBA biology.protein CD8 Spleen |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 174(5) |
| ISSN: | 0022-1767 |
| Popis: | The aryl hydrocarbon receptor (AhR) is a transcription factor belonging to the basic helix-loop-helix-PER-ARNT-SIM superfamily. Xenobiotics, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin, bind the receptor and trigger diverse biological reactions. Thymocyte development and T cell-dependent immune reactions are sensitive targets of AhR-dependent 2,3,7,8-tetrachlorodibenzo-p-dioxin toxicity. However, the exact role of the AhR in T cells in animals exposed to exogenous ligands has not been clarified because indirect effects of activated AhR in other cell types cannot be excluded. In this study, we generated transgenic (Tg) mice expressing a constitutively active mutant of AhR under the regulation of a T cell-specific CD2 promoter to examine AhR function in T cells. The mRNAs of the constitutively active mutant of AhR and an AhR-induced gene, CYP1A1, were expressed in the thymus and spleen of the Tg mice. The transgene expression was clearly detected in the thymocytes, CD4, and CD8 T cells, but not in the B cells or thymus stromal cells. These Tg mice had a decreased number of thymocytes and an increased percentage of CD8 single-positive thymocytes, but their splenocytes were much less affected. By contrast, the increase in number of T cells and B cells taking place in the spleen after immunization was significantly suppressed in the Tg mice. These results clearly show that AhR activation in the T-lineage cells is directly involved in thymocyte loss and skewed differentiation. They also indicate that AhR activation in T cells and not in B cells suppresses the immunization-induced increase in both T cells and B cells. |
| Databáze: | OpenAIRE |
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