Constitutively active aryl hydrocarbon receptor expressed specifically in T-lineage cells causes thymus involution and suppresses the immunization-induced increase in splenocytes

Keiko Nohara, Xiaoqing Pan, Shin Ichi Tsukumo, Azumi Hida, Tomohiro Ito, Haruko Nagai, Kaoru Inouye, Hozumi Motohashi, Masayuki Yamamoto, Yoshiaki Fujii-Kuriyama, Chiharu Tohyama

    Research output: Contribution to journalArticlepeer-review

    56 Citations (Scopus)

    Abstract

    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-tetrachloredibenzo-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.

    Original languageEnglish
    Pages (from-to)2770-2777
    Number of pages8
    JournalJournal of Immunology
    Volume174
    Issue number5
    DOIs
    Publication statusPublished - 2005 Mar 1

    ASJC Scopus subject areas

    • Immunology and Allergy
    • Immunology

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