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

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8 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

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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    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, 195(7), 3129-3138. https://doi.org/10.4049/jimmunol.1302447