| First Author | Bruscoli S | Year | 2015 |
| Journal | Blood | Volume | 126 |
| Issue | 15 | Pages | 1790-801 |
| PubMed ID | 26276664 | Mgi Jnum | J:230683 |
| Mgi Id | MGI:5763536 | Doi | 10.1182/blood-2015-03-631580 |
| Citation | Bruscoli S, et al. (2015) Lack of glucocorticoid-induced leucine zipper (GILZ) deregulates B-cell survival and results in B-cell lymphocytosis in mice. Blood 126(15):1790-801 |
| abstractText | Glucocorticoids (GC) are widely used as antiinflammatory/immunosuppressive drugs and antitumor agents in several types of lymphoma and leukemia. Therapeutic doses of GC induce growth-suppressive and cytotoxic effects on various leukocytes including B cells. Molecular mechanisms of GC action include induction of GC target genes. Glucocorticoid-induced leucine zipper (GILZ) is a rapidly, potently, and invariably GC-induced gene. It mediates a number of GC effects, such as control of cell proliferation, differentiation, and apoptosis. Here we show that deletion of GILZ in mice leads to an accumulation of B lymphocytes in the bone marrow, blood, and lymphoid tissues. Gilz knockout (KO) mice develop a progressive nonlethal B lymphocytosis, with expansion of B220(+) cells in the bone marrow and in the periphery, dependent on increased B-cell survival. Decreased B-cell apoptosis in mice lacking GILZ correlates with increased NF-kappaB transcriptional activity and Bcl-2 expression. B cell-specific gilz KO mice confirmed that the effect of GILZ deletion is B-cell self-intrinsic. These results establish GILZ as an important regulator of B-cell survival and suggest that the deregulation of GILZ expression could be implicated in the pathogenesis of B-cell disorders. |
