Nuclear factor erythroid 2-related factor 2 (Nrf2) is a major transcription factor involved in redox homeostasis and in the response induced by oxidative injury. Nrf2 is present in an inactive state in the cytoplasm of cells. Its activation by internal or external stimuli, such as infections or pollution, leads to the transcription of more than 500 elements through its binding to the antioxidant response element. The lungs are particularly susceptible to factors that generate oxidative stress such as infections, allergens and hyperoxia. Nrf2 has a crucial protective role against these ROS. Oxidative stress and subsequent activation of Nrf2 have been demonstrated in many human respiratory diseases affecting the airways, including asthma and chronic obstructive pulmonary disease (COPD), or the pulmonary parenchyma such as acute respiratory distress syndrome (ARDS) and pulmonary fibrosis. Several compounds, both naturally occurring and synthetic, have been identified as Nrf2 inducers and enhance the activation of Nrf2 and expression of Nrf2-dependent genes. These inducers have proven particularly effective at reducing the severity of the oxidative stress-driven lung injury in various animal models. In humans, these compounds offer promise as potential therapeutic strategies for the management of respiratory pathologies associated with oxidative stress but there is thus far little evidence of efficacy through human trials. The purpose of this review is to summarize the involvement of Nrf2 and its inducers in ARDS, COPD, asthma and lung fibrosis in both human and in experimental models.

SummaryObesity and asthma prevalence has dramatically and concomitantly increased over the last 25 years, and many epidemiological studies have highlighted obesity as an important risk factor for asthma. Although many studies have been performed, the underlying mechanisms remain poorly understood. Innate mechanisms have been involved in both diseases, in particular through the recently described innate lymphoid cells (ILCs). ILCs are subdivided into three groups that are defined by their cytokine production and by their master transcription factor expression, in sharp correlation with their T helper counterparts. However, unlike T helper cells, ILCs do not express antigen-specific receptors, but respond to damage-induced signals. ILCs have been found in target tissues of both diseases, and data have implicated these cells in the pathogenesis of both diseases. In particular group 2 ILCs (ILC2) are activated in both the adipose and lung tissues under the effect of interleukin-33 and interleukin-25 expression. However, counter-intuitively to the well-known association between obesity and asthma, ILC2 are beneficial for obesity but deleterious for asthma. This review will examine the roles of ILCs in each disease and recent data highlighting ILCs as a putative link between obesity and asthma.