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An Enhancer of the IL-7 Receptor α-Chain Locus Controls IL-7 Receptor Expression and Maintenance of Peripheral T Cells.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2015 Oct 01; Vol. 195 (7), pp. 3129-38. Date of Electronic Publication: 2015 Sep 02. - Publication Year :
- 2015
-
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. 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.<br /> (Copyright © 2015 by The American Association of Immunologists, Inc.)
- Subjects :
- Animals
CD4-Positive T-Lymphocytes immunology
CD8-Positive T-Lymphocytes immunology
Cell Differentiation immunology
Cell Proliferation genetics
Cells, Cultured
Dexamethasone pharmacology
Gene Expression drug effects
Gene Expression genetics
Interleukin-7 Receptor alpha Subunit biosynthesis
Lymphocyte Activation immunology
Mice
Mice, Knockout
Promoter Regions, Genetic genetics
Sequence Deletion genetics
Signal Transduction immunology
Transcription, Genetic genetics
Tumor Necrosis Factor-alpha pharmacology
CD4-Positive T-Lymphocytes cytology
CD8-Positive T-Lymphocytes cytology
Enhancer Elements, Genetic
Interleukin-7 Receptor alpha Subunit genetics
Regulatory Sequences, Nucleic Acid genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1550-6606
- Volume :
- 195
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 26336149
- Full Text :
- https://doi.org/10.4049/jimmunol.1302447