Evaluation of Human Endogenous Retroviruses as possible mediators of environmental exposure effects in sistemic sclerosis

This project has been funded thanks to the Joint Call Fondazione Cariplo and Fondazione Telethon 2022 

Systemic sclerosis (SSc) is a rare autoimmune disease characterized by vascular impairment and fibrosis of the skin and multiple internal organs. SSc is defined as a multifactorial disease since is caused by the contribution of different factors. In particular, various environmental factors are associated with SSc onset, such as exposure to airborne pollutants acting together with a genetic predisposition that alone is not able to induce the disease. In this scenario, it is necessary to identify suitable biomarkers able to assess the effects of the environment in triggering SSc. To do this, we propose the methylation of human endogenous retroviruses (HERVs) as a biomarker directly affected by environmental triggers that may have a role in SSc onset. Indeed, the methylation levels of HERV sequences are known to be directly influenced by the environment and are involved in both inflammatory and immune responses that are critical mechanisms underlying SSc pathogenesis. We will measure HERV methylation in patients’ peripheral monocytes and will investigate whether it is influenced by the exposure to different airborne pollutants, such as particulate matter with a diameter of ≤10 and ≤ 2.5 μm, nitrogen dioxide, and ozone experienced by patients up to three years before diagnosis. Moreover, through in vitro studies, we will assess how patients’ monocytes affect endothelial function and fibroblast activation, which are the first and most typical alterations of SSc. The unveiling of the complex interaction between environmental exposure and HERV methylation patterns in SSc patients would dramatically contribute to the understanding of SSc etiology.