An Enhancer of the IL-7 receptor α-chain locus controls IL-7 receptor expression and maintenance of peripheral T cells

Akifumi Abe, Shizue Tani-ichi, Soichiro Shitara, Guangwei Cui, Hisataka Yamada, Hitoshi Miyachi, Satsuki Kitano, Takahiro Hara, Ryo Abe, Yasunobu Yoshikai, Koichi Ikuta

    Research output: Contribution to journalArticle

    4 Citations (Scopus)

    Abstract

    The IL-7R plays critical roles in lymphocyte development and homeostasis. Although IL-7R expression is strictly regulated during lymphocyte differentiation and the immune response, little is known regarding its in vivo regulation. To address this issue, we established a mouse line with targeted deletion of the conserved non-coding sequence 1 (CNS1) element found 3.6 kb upstream of the IL-7Rα promoter. We report that IL-7Rα is expressed normally on T and B cells in thymus and bone marrow of CNS1-/- mice except for in regulatory T cells. In contrast, these mice show reduced IL-7Rα expression in conventional CD4 and CD8 T cells as well as regulatory T, NKT, and γδ T cells in the periphery. CD4 T cells of CNS1-/- mice showed IL-7Rα upregulation in the absence of growth factors and IL-7Rα downregulation by IL-7 or TCR stimulation, although the expression levels were lower than those in control mice. Naive CD4 and CD8 T cells of CNS1-/- mice show attenuated survival by culture with IL-7 and reduced homeostatic proliferation after transfer into lymphopenic hosts. CNS1-/- mice exhibit impaired maintenance of Ag-stimulated T cells. Furthermore, IL-7Rα upregulation by glucocorticoids and TNF-a was abrogated in CNS1-/- mice. This work demonstrates that the CNS1 element controls IL-7Rα expression and maintenance of peripheral T cells, suggesting differential regulation of IL-7Rα expression between central and peripheral lymphoid organs.

    Original languageEnglish
    Pages (from-to)3129-3138
    Number of pages10
    JournalJournal of Immunology
    Volume195
    Issue number7
    DOIs
    Publication statusPublished - Oct 1 2015

    Fingerprint

    Interleukin-7 Receptors
    Internal-External Control
    Maintenance
    T-Lymphocytes
    Interleukin-7
    Up-Regulation
    Lymphocytes
    Natural Killer T-Cells
    Regulatory T-Lymphocytes
    Thymus Gland
    Glucocorticoids
    Intercellular Signaling Peptides and Proteins
    Homeostasis
    B-Lymphocytes
    Down-Regulation
    Bone Marrow

    All Science Journal Classification (ASJC) codes

    • Immunology and Allergy
    • Immunology

    Cite this

    An Enhancer of the IL-7 receptor α-chain locus controls IL-7 receptor expression and maintenance of peripheral T cells. / Abe, Akifumi; Tani-ichi, Shizue; Shitara, Soichiro; Cui, Guangwei; Yamada, Hisataka; Miyachi, Hitoshi; Kitano, Satsuki; Hara, Takahiro; Abe, Ryo; Yoshikai, Yasunobu; Ikuta, Koichi.

    In: Journal of Immunology, Vol. 195, No. 7, 01.10.2015, p. 3129-3138.

    Research output: Contribution to journalArticle

    Abe, A, Tani-ichi, S, Shitara, S, Cui, G, Yamada, H, Miyachi, H, Kitano, S, Hara, T, Abe, R, Yoshikai, Y & Ikuta, K 2015, 'An Enhancer of the IL-7 receptor α-chain locus controls IL-7 receptor expression and maintenance of peripheral T cells', Journal of Immunology, vol. 195, no. 7, pp. 3129-3138. https://doi.org/10.4049/jimmunol.1302447
    Abe, Akifumi ; Tani-ichi, Shizue ; Shitara, Soichiro ; Cui, Guangwei ; Yamada, Hisataka ; Miyachi, Hitoshi ; Kitano, Satsuki ; Hara, Takahiro ; Abe, Ryo ; Yoshikai, Yasunobu ; Ikuta, Koichi. / An Enhancer of the IL-7 receptor α-chain locus controls IL-7 receptor expression and maintenance of peripheral T cells. In: Journal of Immunology. 2015 ; Vol. 195, No. 7. pp. 3129-3138.
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