ABSTRACT
Title
Glucocorticoid-Induced Leucine Zipper (GILZ) controls T lymphocytes differentiation
Authors
O. Bereshchenko1, M. Coppo1, M. Cimino1, M. Di Sante1, A. Venanzi1, S. Bruscoli1and C. Riccardi1
1Dept. of Clinical and Experimental Medicine, Section of Pharmacology, University of Perugia, Italy.
1Dept. of Clinical and Experimental Medicine, Section of Pharmacology, University of Perugia, Italy.
Abstract
GILZ (Glucocorticoid-Induced Leucine Zipper), a gene rapidly induced by dexamethasone, mediates some of the Glucocorticoid(GC)-induced effects and is involved in control of many cell functions including cell growth and differentiation. Most of these effects are due to GILZ interaction with NF-kB and MAPK pathway components. Using T-cell specific GILZ KO mice, we demonstrate GILZ is implicated in regulation of T lymphocytes development.
In particular we evaluated the development of Th1, Th2, Th9 and Th17 CD4+ subpopulations. After in vitro differentiation of peripheral naïve CD4+ T, cells from GILZ KO and wild type (WT) littermates mice we detected an imbalance of differentiation of cell subpopulation as well of cytokine production. In particular, cells from GILZ KO mice showed an increased Th1 response in vitro as evaluated by qPCR and flow cytometry analysis. Moreover, consequent to this GILZ-mediated Th1 polarization we found an increased susceptibility to inflammatory process development in vivo. In fact, using a colitis experimental model, we found an augmented disease induction in GILZ KO mice as compared to WT littermates. Evaluation of clinical score, macroscopic and microscopic analysis on intestine indicated the major Th1 response contributing to increased disease in GILZ KO mice.
In conclusion, these results indicate that GILZ contributes to T lymphocytes differentiation and mediates the immuno-regulatory effect of GC.
In particular we evaluated the development of Th1, Th2, Th9 and Th17 CD4+ subpopulations. After in vitro differentiation of peripheral naïve CD4+ T, cells from GILZ KO and wild type (WT) littermates mice we detected an imbalance of differentiation of cell subpopulation as well of cytokine production. In particular, cells from GILZ KO mice showed an increased Th1 response in vitro as evaluated by qPCR and flow cytometry analysis. Moreover, consequent to this GILZ-mediated Th1 polarization we found an increased susceptibility to inflammatory process development in vivo. In fact, using a colitis experimental model, we found an augmented disease induction in GILZ KO mice as compared to WT littermates. Evaluation of clinical score, macroscopic and microscopic analysis on intestine indicated the major Th1 response contributing to increased disease in GILZ KO mice.
In conclusion, these results indicate that GILZ contributes to T lymphocytes differentiation and mediates the immuno-regulatory effect of GC.