Air pollution as a causal factor in immune dysregulation behind membranous nephropathy – AIRGEM

Air pollution is currently the subject of many recommendations to limit its adverse effects on human health. It has been shown to induce the production of pro-inflammatory cytokines – e.g., interleukin (IL) 1ß, IL-6. Many studies have observed an association between the emergence of autoimmune diseases and air pollution. Immune-mediated conditions are thought to result from a complex interplay between genetic predisposition, immune dysregulation, and environmental factors. Membranous nephropathy (MN) is a rare autoimmune disease induced by auto-antibodies directed against podocyte proteins with an increasing incidence during the last decades. Epidemiological studies have shown an interplay between air pollution exposure and MN incidence. Very few prospective studies have focused on the impact of air pollution on the immune system orientation in real life conditions and the impact of this orientation on the emergence of autoimmune diseases or in experimental conditions on podocyte function.
We hypothesize that air pollution triggers immune dysregulation favoring Th17 signaling which in turn promotes the onset of MN. We will carry out a prospective study and original in vitro approaches that will allow us to refine the data related to the role of exposure to air pollutants on Th17-prone deregulation and MN susceptibility. In addition, we will use in vivo models to determine to which extent exposure to air pollutants drives Th17-mediated tissue inflammation. Finally, we will determine how air pollutants directly deregulate podocytes and lung epithelium.