R. Leinardi, L. Hiéronimus, C. Longo Sanchez-Calero, F. Huaux
The current research program of our group is dedicated to deciphering the impact of micrometric and nanometric particles on the immune system and human health with a particular focus on particle-induced chronic diseases (inflammation, granuloma formation, fibrosis and cancer). We are implicated in translational studies with patients and develop relevant in vitro and in vivo models to investigate particle toxicity.
Immunosuppression as a driving force of granuloma formation and fibrosis (PhD of Léa Hironimous)
Our experimental studies have revealed that inhaled micro- and nano-particles induce an uncontrolled immunosuppression characterized by the release of potent anti-inflammatory cytokines and the recruitment of immunoregulatory macrophages and lymphocytes. This persistent immunosuppressive environment is initially established to limit deleterious inflammation but contributes later to granuloma and fibrosis by promoting fibroblast proliferation and matrix element synthesis. Our current observations on macrophages and lymphocytes challenge the conventional inflammatory theory and indicate that the emergence of particle-related fibrotic disorders may result from non-inflammatory events (DOI: 10.3389/fimmu.2018.02364). This research is granted by FNRS.
Carbon nanotubes to study mesothelioma (Riccardo Leinardi)
Malignant mesothelioma is a cancer caused by needle-like shape particles (i.e. asbestos and carbon nanotubes). Its prognosis is poor and current therapies remain ineffective. In the frame of a “Fondation contre le Cancer” grant, we experimentally showed that macrophages dying after carbon nanotube phagocytosis are replenished by monocytic-derived cells that promote an early immunosuppressive environment favoring tumoral cell evasion from T cell surveillance (DOI: 10.3390/app10134513). We are now determining which immune mediator released by these macrophages subverts early immune surveillance against transformed cells.
Particles exacerbate autoimmune diseases (PhD of Chiara Longo)
Occupational exposure to inorganic particles exacerbates the development of systemic autoimmune diseases. We are currently investigating the mechanism by which particles contribute to the breakdown of self-tolerance. Our experimental data suggest that particle cytotoxicity results in self-antigen accumulation (e.g. nuclear proteins and DNA) which activates innate and adaptive immunity and autoantibody production. We are involved in the H2020 EXIMIOUS project which allows us to extrapolate our experimental findings in human by examining samples from particle-exposed patients and workers.
Matzinger theory explains particle-induced immune responses (Riccardo Leinardi)
We scrutinize the danger model of the immunologist Polly Matzinger in particle toxicology and investigate whether damaged cells and the subsequent release of immunogenic endogenous signals (e.g. alarmins) can trigger immune responses (DOI: 10.1186/s12989-014-0069-x). Recently, we found that the defective ability of the body to clear immunogenic death cells (efferocytosis) results in fibrosis after particles. This program is sponsored by ANSES.