Abstract
Glucocorticoid-induced leucine zipper (GILZ) is transcriptionally upregulated by glucocorticoids (GCs) and mediates many of the anti-inflammatory effects of GCs. Since B cell activity has been linked to cytokine production and modulation of inflammatory responses, we herein investigated the role of GILZ in B cells during colitis development. B cell-specific gilz knock-out (gilz B cKO) mice exhibited increased production of the pro-inflammatory cytokine IFN-γ in B cells, and consequently CD4+ T cell activation. Increased IFN-γ production in B cells was associated with enhanced transcriptional activity of the transcription factor activator protein-1 (AP-1) on the IFN-γ promoter. Moreover, GILZ deficiency in B cells was linked to enhanced susceptibility to experimental colitis in mice, and this was reversed by administering GILZ protein. Interestingly, we observed increased production of IFN-γ in both B and T cells infiltrating the lamina propria (LP) of gilz B cKO mice. Together, these findings indicate that GILZ controls IFN-γ production in B cells, which also affects T cell activity, and increased production of IFN-γ by B and T cells in LP is associated with predisposition to inflammatory colitis in mice.
Highlights
Glucocorticoids (GCs) have anti-inflammatory and immunosuppressive activities that involve most branches of the inflammatory responses
As observed for mice with glucocorticoid-induced leucine zipper (GILZ) deletion in all tissues [28], total white blood cell (WBC) and lymphocyte counts were increased in the peripheral blood of gilz B cell conditional gilz KO (B cKO) mice compared with WT mice (Figure 1A)
These results demonstrate that the increase in the number of B cells following B cell-specific GILZ deletion in gilz B cKO mice is cell-intrinsic to the B cell population
Summary
Glucocorticoids (GCs) have anti-inflammatory and immunosuppressive activities that involve most branches of the inflammatory responses. GCs are potent anti-inflammatory drugs, their clinical effects are transitory and chronic use is accompanied by serious side effects that necessitate discontinuation of therapy [1, 2]. The gene encoding glucocorticoid-induced leucine zipper (GILZ) is rapidly induced by dexamethasone (DEX), a synthetic GC [3, 4], and GILZ has been shown to mediate the anti-inflammatory activity of GCs [5,6,7,8,9]. GILZ modulates the same immune response- and inflammation-related signaling pathways implicated in GC-induced anti-inflammatory and immunosuppressive activities, suggesting that GILZ-based strategies can constitute a new approach for the treatment of inflammatory/autoimmune diseases.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
