Positive effects of glucocorticoids on T cell function by up-regulation of IL-7 receptor alpha.
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.
Franchimont
Denis
D
Lymphocyte Cell Biology Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Galon
Jérôme
J
Vacchio
Melanie S
MS
Fan
Samuel
S
Visconti
Roberta
R
Frucht
David M
DM
Geenen
Vincent
V
Chrousos
George P
GP
Ashwell
Jonathan D
JD
O'Shea
John J
JJ
D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D004357:Drug Synergism; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D015851:Interleukin-7 / Q000494:pharmacology; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000096:biosynthesis; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D020395:Receptors, Interleukin-7 / Q000096:biosynthesis* / Q000235:genetics; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D015533:Transcriptional Activation; D015854:Up-Regulation
D005938:Glucocorticoids; D015851:Interleukin-7; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2; D020395:Receptors, Interleukin-7; C415350:interleukin-7 receptor, alpha chain; D003907:Dexamethasone