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Redox regulation of the immune response

Cellular & Molecular Immunology 2022年第10期19卷 1079-1101页

作者： Gerwyn Morris Maria Gevezova victoria sarafian Michael Maes Deakin University IMPACT-the Institute for Mental and Physical Health and Clinical TranslationSchool of MedicineBarwon HealthGeelongVICAustralia Department of Medical Biology Medical University-PlovdivPlovdivBulgaria Research Institute at Medical University-Plovdiv PlovdivBulgaria Department of Psychiatry Faculty of MedicineKing Chulalongkorn Memorial HospitalBangkokThailand Department of Psychiatry Medical University of PlovdivPlovdivBulgaria

The immune-inflammatory response is associated with increased nitro-oxidative stress.The aim of this mechanistic review is to examine:(a)the role of redox-sensitive transcription factors and enzymes,ROS/RNS production,and the activity of cellular antioxidants in the activation and performance of macrophages,dendritic cells,neutrophils,T-cells,B-cells,and natural killer cells;(b)the involvement of high-density lipoprotein(HDL),apolipoprotein A1(ApoA1),paraoxonase-1(PON1),and oxidized phospholipids in regulating the immune response;and(c)the detrimental effects of hypernitrosylation and chronic nitro-oxidative stress on the immune response.The redox changes during immune-inflammatory responses are orchestrated by the actions of nuclear factor-κB,HIF1α,the mechanistic target of rapamycin,the phosphatidylinositol 3-kinase/protein kinase B signaling pathway,mitogen-activated protein kinases,5'AMP-activated protein kinase,and peroxisome proliferator-activated receptor.The performance and survival of individual immune cells is under redox control and depends on intracellular and extracellular levels of ROS/RNS.They are heavily influenced by cellular antioxidants including the glutathione and thioredoxin systems,nuclear factor erythroid 2-related factor 2,and the HDL/ApoA1/PON1 complex.Chronic nitro-oxidative stress and hypernitrosylation inhibit the activity of those antioxidant systems,the tricarboxylic acid cycle,mitochondrial functions,and the metabolism of immune cells.In conclusion,redox-associated mechanisms modulate metabolic reprogramming of immune cells,macrophage and T helper cell polarization,phagocytosis,production of pro-versus anti-inflammatory cytokines,immune training and tolerance,chemotaxis,pathogen sensing,antiviral and antibacterial effects,Toll-like receptor activity,and endotoxin tolerance.

关键词： Oxidative and nitrosative stress Immune response Inflammation Antioxidants Physiological stres

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