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

A Abe, S Tani-ichi, S Shitara, G Cui… - The Journal of …, 2015 - journals.aai.org
A Abe, S Tani-ichi, S Shitara, G Cui, H Yamada, H Miyachi, S Kitano, T Hara, R Abe…
The Journal of Immunology, 2015journals.aai.org
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 …
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.
journals.aai.org