Glucocorticoids and Glucocorticoid-Induced-Leucine-Zipper (GILZ) in Psoriasis
- PMID: 31572404
- PMCID: PMC6753639
- DOI: 10.3389/fimmu.2019.02220
Glucocorticoids and Glucocorticoid-Induced-Leucine-Zipper (GILZ) in Psoriasis
Abstract
Psoriasis is a prevalent chronic inflammatory human disease initiated by impaired function of immune cells and epidermal keratinocytes, resulting in increased cytokine production and hyperproliferation, leading to skin lesions. Overproduction of Th1- and Th17-cytokines including interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-23, IL-17, and IL-22, is a major driver of the disease. Glucocorticoids (GCs) represent the mainstay protocol for treating psoriasis as they modulate epidermal differentiation and are potent anti-inflammatory compounds. The development of safer GC-based therapies is a high priority due to potentially severe adverse effects associated with prolonged GC use. Specific efforts have focused on downstream anti-inflammatory effectors of GC-signaling such as GC-Induced-Leucine-Zipper (GILZ), which suppresses Th17 responses and antagonizes multiple pro-inflammatory signaling pathways involved in psoriasis, including AP-1, NF-κB, STAT3, and ROR-γt. Here we review evidence regarding defective GC signaling, GC receptor (GR) function, and GILZ in psoriasis. We discuss seemingly contradicting data on the loss- and gain-of-function of GILZ in the imiquimod-induced mouse model of psoriasis. We also present potential therapeutic strategies aimed to restore GC-related pathways.
Keywords: glucocorticoid-induced-leucine-zipper (GILZ/TSC22D3); glucocorticoids (GCs); immune cells; keratinocytes; psoriasis; signaling; skin inflammation.
Copyright © 2019 Sevilla and Pérez.
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