Glucocorticoid-induced leucine zipper protein (GILZ)

Glucocorticoid-induced leucine zipper protein (GILZ), encoded by the TSC22D3 gene, is a leucine zipper-class transcriptional regulator essential for mediating the anti-inflammatory and immunosuppressive effects of glucocorticoids and interleukin-10. GILZ is ubiquitously expressed and rapidly induced in immune cells, where it exerts its action primarily by inhibiting inflammatory transcription factors (NF-κB, AP-1) and modulating kinase signaling, thereby reducing pro-inflammatory cytokine production and promoting regulatory T cell differentiation. Beyond immune regulation, GILZ controls cellular proliferation, apoptosis, oncogenic signaling, sodium ion channel transport, and physiological stress responses in tissues such as the kidney, adipose tissue, and the brain. Dysregulation of GILZ is implicated in cancer, chronic inflammation, metabolic and neuropsychiatric disorders, and cardiovascular disease. While glucocorticoids stimulate GILZ expression for therapeutic immunosuppression, overactivation may lead to increased infection risk and suppression of anticancer immunity.

Other names

TSC22 domain family member 3TSC22D3DSIPIProtein DIPhDIPTSC-22RDIPTSC22 domain family protein 3DSIP-immunoreactive peptideDelta sleep-inducing peptide immunoreactorTSC-22-like proteinTSC-22-related proteinDSIP-immunoreactive leucine zipper proteinGILZ

Induction of GILZ/GILZ isoforms via activation of glucocorticoid receptor, resulting in suppression of pro-inflammatory transcription factors (NF-κB, AP-1). Modulation of anti-apoptotic and pro-apoptotic signaling in immune and epithelial cells. Reduction of cytokine production, immune cell activation, and effector responses.