Figure 1.

GILZ expression correlates with monocyte/macrophage activation state and functions. (A). GC or IL-10 induce high GILZ expression levels, inducing the resting state in these cells. Low GILZ expression allows macrophages to activate and initiate phagocytic activity. (B). GILZ is a target of ANXA1 and cannot be fully induced by GC in the absence of ANXA1, with subsequent release of proinflammatory cytokines. Conversely, ANXA1 induction favors GILZ expression, driving macrophages to a state of tolerance, reducing proinflammatory cytokine expression, and inducing unresponsiveness to LPS exposure. (C). Depending on the stimulating cytokines released by Th-specific cells, macrophages exist under two distinct phenotypes: the proinflammatory M1 and the anti-inflammatory M2. GILZ expression is low in M1 macrophages and is high in M2 cells, with consequent raised capability for efferocytosis. (D). GILZ ablation in GILZ-KO mice confers an activated phenotype to the macrophages of young mice that is very similar to those of old WT mice, which are macrophages prone to causing inflammation, i.e., inflammaging. In the LPS-resistant SPRET/Ei mouse strain, GILZ is expressed at abnormally high levels in macrophages, which show a tolerogenic phenotype.