Background – Sjӧgren Syndrome (SS) is a systemic autoimmune disease characterized by inflammation of lacrimal and salivary glands (SG). SG epithelial cells (SGEC) play a key role in sustaining inflammation in SS. However, the mechanisms responsible for the inflammatory activation of SGEC remain largely undetermined. Our line of research indicates that SGECs in SS exhibit profound changes in cell energy metabolism (eg, increased autophagy, glycolysis, and TCA cycle activation), as well as downstream upregulation of adhesion molecules and increased cytokine production (eg, IL-6). Based on these findings, we hypothesize that altered cell energy metabolism of SGEC is a central and targetable driver of SG inflammation in SS.
AIM 1: to dissect the metabolic activation of SGECs in SS.
AIM 2: to dissect the pro-inflammatory epigenetic changes in SGECs.
AIM 3: to determine the therapeutic potential of targeting SGEC energy metabolism.
Milestone 1, Month 12 (AIM 1): characterization of metabolic activation of SGECs in SS.
Milestone 2, Month 24 (AIM 2): characterization of epigenetic changes in SS SGECs.
Milestone 3, Month 36 (AIM 3): testing of strategies suppressing SGECs inflammatory activation.
ANIMASS (Associazione Nazionale Italiana Malati Sindrome di Sjogren) is the main non-profit SS patient association in Italy (http://www.animass.org/AMRI). ANIMASS had a key role in informing the priorities of the present research study: specifically, the lack of effective therapies to restore secretory function was perceived as a critically unmet need by SS patients, who strongly advocated for the development of therapeutic alternatives to the currently available but scarcely effective immunotherapies. Tight and productive collaborative ties between our Institution and ANIMASS will be key to the conduction of this study and will ensure constant referral of individuals with suspected SS to our dedicated Clinic, as well as active involvement in outreach activities.