| First Author | Abe A | Year | 2015 |
| Journal | J Immunol | Volume | 195 |
| Issue | 7 | Pages | 3129-38 |
| PubMed ID | 26336149 | Mgi Jnum | J:333539 |
| Mgi Id | MGI:6843984 | Doi | 10.4049/jimmunol.1302447 |
| Citation | Abe A, et al. (2015) An Enhancer of the IL-7 Receptor alpha-Chain Locus Controls IL-7 Receptor Expression and Maintenance of Peripheral T Cells. J Immunol 195(7):3129-38 |
| abstractText | 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-7Ralpha promoter. We report that IL-7Ralpha 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-7Ralpha expression in conventional CD4 and CD8 T cells as well as regulatory T, NKT, and gammadelta T cells in the periphery. CD4 T cells of CNS1(-/-) mice showed IL-7Ralpha upregulation in the absence of growth factors and IL-7Ralpha 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-7Ralpha upregulation by glucocorticoids and TNF-alpha was abrogated in CNS1(-/-) mice. This work demonstrates that the CNS1 element controls IL-7Ralpha expression and maintenance of peripheral T cells, suggesting differential regulation of IL-7Ralpha expression between central and peripheral lymphoid organs. |
