MANFRE' Valeria

depositphotos_137014128-stock-illustration-user-profile-icon.jpg Supervisore: Prof. Quartuccio
Evaluation of the secretagogue effect of PDE4 inhibitors on human salivary gland organoids obtained from primary Sjögren’s syndrome patients
Up to date, evidence of effective treatment for dry mouth symptoms in primary Sjögren’s syndrome (pSS) is lacking. Obtaining functional salivary gland organoids from patients affected by pSS might help elucidate its pathogenesis and detect new therapeutic targets and agents for treating glandular manifestations. Saliva production is a complex process, and one of its fundamental mediators is intracellular cAMP (i-cAMP). It controls the action of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) in salivary epithelium, whose malfunction is postulated in pSS pathogenesis. Phosphodiesterase type 4 (PDE4) is instead responsible of i-cAMP deregulation, and PDE4 inhibition might stimulate salivary function in pSS, as shown by mice models. Thus, the aims of this project are: the obtainment of vital and functional salivary gland organoids from pSS patients; the establishment of their morphological structure, regenerative and functional capacity, and differentiative potential in basal condition and after stimulation with drugs such as PDE4 inhibitors (e.g. Apremilast), active on CFTR channel through i-cAMP increase, to test their secretagogue ability of stimulating in vitro saliva production on pSS salivary gland organoids. A further step will be the creation of complex co-culture systems of salivary epithelium and peripheral blood mononucleate cells to shed light on the interplay between these components in pSS pathogenesis and its related lymphoproliferative complications.