Positive effects of glucocorticoids on T cell function by up-regulation of IL-7 receptor alpha |
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Authors: | Franchimont Denis Galon Jérôme Vacchio Melanie S Fan Samuel Visconti Roberta Frucht David M Geenen Vincent Chrousos George P Ashwell Jonathan D O'Shea John J |
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Institution: | Lymphocyte Cell Biology Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. |
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Abstract: | Despite the effects of glucocorticoids on immune function, relatively little is known about glucocorticoid-inducible genes and how their products may regulate lymphocyte function. Using DNA microarray technology to analyze gene expression in PBMC from healthy donors, we identified IL-7Ralpha as a glucocorticoid-inducible gene. This observation was confirmed at the mRNA and protein levels. Conversely, TCR signaling decreased IL-7Ralpha expression, and the relative strength of signaling between these two receptors determined the final IL-7Ralpha levels. The up-regulation of IL-7Ralpha by glucocorticoids was associated with enhanced IL-7-mediated signaling and function. Moreover, IL-7-mediated inhibition of apoptosis at increasing concentrations of glucocorticoids is consistent with enhanced cell sensitivity to IL-7 following glucocorticoid exposure. These observations provide a mechanism by which glucocorticoids may have a positive influence on T cell survival and function. |
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