An Enhancer of the IL-7 Receptor α-Chain Locus Controls IL-7 Receptor Expression and Maintenance of Peripheral T Cells

The Journal of Immunology : Official Journal of the American Association of Immunologists
Akifumi AbeKoichi Ikuta

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-α was abrogated in CNS1(-/-) mice. Thi...Continue Reading

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Citations

May 29, 2019·Wiley Interdisciplinary Reviews. Systems Biology and Medicine·Jung-Hyun ParkCarmen Molina-París
Nov 7, 2019·The Journal of Clinical Investigation·Lauren K MeyerMichelle L Hermiston
Jan 12, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Guangwei CuiKoichi Ikuta
Jul 28, 2020·International Immunology·Akihiro Shimba, Koichi Ikuta
Dec 19, 2019·Genome Medicine·Filipa Rijo-Ferreira, Joseph S Takahashi
Mar 21, 2020·Proceedings of the National Academy of Sciences of the United States of America·Mengliang YeElina Zueva
Oct 20, 2020·Frontiers in Immunology·Akihiro Shimba, Koichi Ikuta
Nov 22, 2020·Seminars in Immunopathology·Akihiro Shimba, Koichi Ikuta
Mar 19, 2021·Journal of Cellular and Molecular Medicine·Lei LeiBaojun Zhang

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