Journal Article

Unraveling the Role of Reactive Oxygen Species in T Lymphocyte Signaling

Heumann, Philipp, Kunst, Claudia, Schmid, Stephan, Müller, Martina, Tümen, Deniz, Gülow, Karsten, Kandulski, Arne

2024

Overview

Reactive oxygen species (ROS) are central to inter- and intracellular signaling. Their localized and transient effects are due to their short half-life, especially when generated in controlled amounts. Upon T cell receptor (TCR) activation, regulated ROS signaling is primarily initiated by complexes I and III of the electron transport chain (ETC). Subsequent ROS production triggers the activation of nicotinamide adenine dinucleotide phosphate oxidase 2 (NADPH oxidase 2), prolonging the oxidative signal. This signal then engages kinase signaling cascades such as the mitogen-activated protein kinase (MAPK) pathway and increases the activity of REDOX-sensitive transcription factors such as nuclear factor-kappa B (NF-κB) and activator protein-1 (AP-1). To limit ROS overproduction and prevent oxidative stress, nuclear factor erythroid 2-related factor 2 (Nrf2) and antioxidant proteins such as superoxide dismutases (SODs) finely regulate signal intensity and are capable of terminating the oxidative signal when needed. Thus, oxidative signals, such as T cell activation, are well-controlled and critical for cellular communication.

• Publisher: MDPI AG,MDPI
• Subject: Adapter proteins / Animals / Antigens / Antioxidants / B cells / DNA binding proteins / Electron transport / Endoplasmic reticulum / Enzymes / Humans / Kinases / Lymphocyte Activation / Lymphocytes / Membranes / Mitochondria / Mitogens / NF-E2-Related Factor 2 - metabolism / Niacinamide / Oxidases / Oxidation-Reduction / Oxidative Stress / Plasma / Protein kinases / Reactive oxygen species / Reactive Oxygen Species - metabolism / Receptors, Antigen, T-Cell - metabolism / Review / Signal Transduction / Superoxide / T cell receptors / T cells / T-Lymphocytes - immunology / T-Lymphocytes - metabolism / Thymus gland