A gradient of glucocorticoid sensitivity among helper T cell cytokines. (October 2016)

• Record Type: Journal Article
• Authors: Banuelos, Jesus; Lu, Nicholas Z.
• Is Part Of: Cytokine & growth factor reviews. Volume 31(2016)
• Page Start: 27
• Page End: 35
• Publication Date: 2016-10
• Subjects: ADAM17 ADAM Metallopeptidase Domain 17 -- ADH alcohol dehydrogenase -- AHR aryl hydrocarbon receptor -- AP-1 activator protein 1 -- BCL B-cell lymphoma -- BIM Bcl-2 interacting mediator of cell death -- CBP CREB-binding protein -- CCL CC chemokine ligands -- CXCL CXC chemokine ligand -- CXCR CXC chemokine receptors -- DBD DNA-binding domain -- DEX dexamethasone -- FKBP FK506 binding protein -- FOXP3 forkhead box P3 -- GATA-3 GATA binding protein 3 -- G-CSF granulocyte-colony stimulating factor -- GM-CSF granulocyte-macrophage colony-stimulating factor -- GR glucocorticoid receptor -- GRE glucocorticoid response element -- HDAC histone deacetylase -- HSP heat shock protein -- IFNγ interferon γ -- Ig immunoglobulin -- IκBα NF-κB inhibitor α -- IκBζ NF-κB inhibitor ζ -- IL interleukin -- IR-nGRE inverted repeat negative glucocorticoid response element -- LBD ligand binding domain -- LPS lipopolysaccharide -- MAP mitogen-activated protein -- MHC major histocompatibility complex -- MIP macrophage inflammatory protein -- MMTV mouse mammary tumor virus -- NCoR nuclear receptor co-repressor -- NF-κB nuclear factor kappa-light-chain-enhancer of activated B cells -- NTD N-terminal domain -- PBMC peripheral blood mononuclear cells -- Pol II RNA polymerase II -- RORγt RAR-related orphan receptor γ -- SMRT silencing mediator for retinoid and thyroid hormone receptors -- SOCS suppressor of cytokine signaling -- STAT signal transducer and activator of transcription -- TAT tyrosine aminotransferase 3 -- T-BET T-box expressed in T cells -- Tfh follicular helper T cell -- TGF-β transforming growth factor β -- Th helper T cell -- TLR toll-like receptor -- TNF tumor necrosis factor -- Treg regulatory T cells -- TSLP thymic stromal lymphopoietin; Glucocorticoid -- Th1 -- Th2 -- Th17 -- IL-17; Cytokines -- Periodicals; 571.84
• DOI: 10.1016/j.cytogfr.2016.05.002
• Languages: English
• ISSNs: 1359-6101

Abstract

Highlights: Th1 cells are sensitive to glucocorticoid-induced apoptosis and cytokine suppression. Th2 cells are sensitive to glucocorticoid suppression of cytokines but resistant to glucocorticoid-induced apoptosis. Th17 cells are resistant to glucocorticoid-induced apoptosis and cytokine suppression. Underlying Th cells mediate distinct glucocorticoid responsiveness and severity of diseases. Th cells have cell and promoter-specific glucocorticoid receptor signaling. Abstract: Helper T (Th) cells secret specific cytokines that promote immune responses whereas glucocorticoids limit the extent of immune responses by inhibiting cytokine secretion and other functions of Th cells. However, glucocorticoid resistance develops in subgroups of patients with Th cell-driven diseases such as asthma and Crohn's disease. Recent evidence supports that Th1, Th2, and Th17 cells have distinct glucocorticoid sensitivity. Th1 cells are sensitive to glucocorticoid-induced apoptosis and cytokine suppression while Th2 cells are sensitive to the latter but not the former and Th17 cells are resistant to both. This gradient of glucocorticoid sensitivity of Th cells corresponds to the glucocorticoid sensitivity of the diseases they underlie. We identify the mechanisms contributing to distinct glucocorticoid sensitivity of Th cells and their cytokines in the literature, as this information is useful to improve treatment strategies for glucocorticoid resistant immunological disorders.