Immunity and Immunodeficiency Lab
Our lab aims to understand how adaptive immunity interacts with tissue microenvironment components – including microbiota at barrier sites – in the development of bacterial infections and tumorigenesis, as well as primary immune deficiencies (PIDs).
There is increasing evidence that disruption/dysregulation of the adaptive immune system interacts with tissue microenvironment, including microbiota, to contribute to the progression of diseases such as immunodeficiency and autoimmunity, resistant bacterial infections and tumors. Understanding these complex relationships could be exploited to identify therapeutic targets and define novel therapies that are relevant for different clinical settings and challenges. To accomplish this goal, we combine immunological studies in patients, relevant disease and infectious models, as well as state-of-the-art high-throughput technologies.
Main research areas
Role of host-microbiota interactions in the pathogenesis of primary immune deficiencies
Most genetic defects causing primary immune deficiencies (PID) lead also to perturbations in immune surveillance at the intestinal barrier, uncovering non-redundant pathways required for intestinal colonization by critical commensals. Consistently, a substantial proportion of PID patients presents with clinically challenging inflammatory bowel disease-like pathology. In our lab we focused on two PID, Omenn syndrome and Chronic Granulomatous Disease, and demonstrated that dysbiosis and loss of tolerance to commensals have a substantial role in determining the distinctive immune dysregulation and inflammatory processes.
Understanding the mechanisms controlling host-microbe interactions during bacterial infections
Disease tolerance and resistance are two mechanisms used by multicellular organisms to control tissue damage induced by an infection. Understanding how these two branches of the host response regulate each other or the conditions in which one prevails over the other is of fundamental importance to fight infections while preserving tissue integrity. We identified Dipeptidyl peptidase 3 (DPP3), a cytosolic ubiquitous metallopeptidase involved in the hydrolysis of many bioactive peptides, as a key player in the regulation of disease tolerance and resistance during K. pneumoniae infections.
Dissecting the interplay between adaptive responses and cellular senescence in tumorigenesis
Hepatocellular carcinoma (HCC) is a frequent neoplasia and a leading cause of inflammation‐related cancer mortality. Despite that most HCCs arise from persistent inflammatory conditions, pathways linking chronic inflammation to cancer development are still incompletely elucidated. We recently demonstrated that adaptive immunity sustains liver fibrosis and favors HCC growth in chronic injury, by modulating innate components of inflammation and limiting the extent of hepatic stellate cells’ cellular senescence.