NADPH Oxidase Deficiency: A Multisystem Approach

Abstract

The immune system is a complex system able to recognize a wide variety of host agents, through different biological processes. For example, controlled changes in the redox state are able to start different pathways in immune cells and are involved in the killing of microbes. The generation and release of ROS in the form of an “oxidative burst” represent the pivotal mechanism by which phagocytic cells are able to destroy pathogens. On the other hand, impaired oxidative balance is also implicated in the pathogenesis of inflammatory complications, which may affect the function of many body systems. NADPH oxidase (NOX) plays a pivotal role in the production of ROS, and the defect of its different subunits leads to the development of chronic granulomatous disease (CGD). The defect of the different NOX subunits in CGD affects different organs. In this context, this review will be focused on the description of the effect of NOX2 deficiency in different body systems. Moreover, we will also focus our attention on the novel insight in the pathogenesis of immunodeficiency and inflammation-related manifestations and on the protective role of NOX2 deficiency against the development of atherosclerosis.

The Hematopoietic Oxidase NOX2 Regulates Self-Renewal of Leukemic Stem Cells

“…In the hematopoietic system, deficiency of either NOX2 or the GTPase RAC proteins significantly perturbs the normal balance of blood cell production and limits the self-renewal potential of HSCs (Cancelas et al, 2005; Roberts et al, 1999; Weisser et al, 2016; Yang et al, 2007). Moreover, loss-of-function mutations in genes encoding several subunits of the enzyme are causal for chronic granulomatous disease, a rare inherited immunodeficiency syndrome with an estimated frequency of 1/200,000 to 1/250,000 newborns (Giardino et al, 2017). A number of studies aimed at understanding the role of NADPH oxidases in the settings of malignant tumors have also uncovered some aspects of their function.…”

Chronic lung inflammation and pulmonary fibrosis after multiple intranasal instillation of PM2.5 in mice

“…NOX4 is the only member of NADPH oxidase family which is localized in mitochondria, and contributes to mtROS levels [38]. NOX4 can be stimulated by TGFβ1-SMAD2/3 pathways to catalyze the production of ROS, and can drive fibroblast proliferation and differentiation [39,40].…”

The ACE rs4340 polymorphism as genetic modulator of gender-specific trends in diabetic ketoacidosis development at onset of type 1 diabetes in children.

“…2,5 Above uncoupling, could lead to dysfunction of suppressive CD8+ T regulatory cells (CD8+ Treg) further exacerbated by DKA and thus to more aggressive autoimmune destruction of β-cells at the onset of T1DM associated with DKA presentation. 18,19 Significant differences in HbA1c level dynamics noticed in male carriers of genotypes DD+ID depending on the DKA occurrence at T1DM diagnosis could be explained by the male-predominant expression of PEPCK, which is further upregulated in renal proximal tubule and hepatocytes under conditions of prolonged metabolic acidosis, leading to the exacerbation of hyperglycemia associated with insulin deficiency. 2,6,8…”