Pos0809 harnessing cell energy metabolism to suppress salivary gland inflammation in sjögren syndrome

Background SG epithelial cells (SGEC) play a key role in sustaining inflammation in Sjӧgren Syndrome (SS), which is indeed termed an ‘autoimmune epithelitis’. 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 as indicated by aberrant expression of autophagy [1]. Inhibitions of autophagic process results in a down regulation of SGECs activation [1], thus indicating a crucial role of SGEC energy metabolism in the induction of autoimmune epithelitis. Objectives Aim of this study is to characterize metabolic changes occurring in SS SGECs and dissect the link between these changes and their acquired pro-inflammatory function. Methods SGECs were isolated from minor SG biopsies deriving from patients with SS and sicca. Intracellular metabolomic analysis was performed on direct ex vivo isolated primary SGECs. As read out of functional activation of SS SGECs, supernatants from SGECs coltures were collected to perform ELISA test in order to evaluate the expression of the pro-inflammatory mediator IL-6. Results Principal component analysis (PCA) of high-throughput metabolomics analysis of sicca (n=7) and SS (n=7) SGECs revealed a separation along the component 1 axis (46.6% of variance) indicating profound differences in the intracellular metabolome ( Figure 1a ). Unsupervised clustering analysis of metabolites revealed profound metabolic differences between SS and (n=7) sicca (n=7) SGECs ( Figure 1b ). Analysis of selected metabolites confirmed a shift towards increased glycolysis and TCA cycle activation in SS SGECs ( Figure 1c ). Supernatant concentrations of IL-6 were higher in SS (n=21) compared to sicca (n=14) SGECs ( Figure 1d ). Conclusion SGECs from SS patients display altered cell energy metabolism with evidence of increased glycolysis and activated TCA cycle. A metabolic driven pro-inflammatory status of SS SGECs seems confirmed by increased basal expression of IL-6. Validation of our metabolomic results, along with transcriptomic and epigenetic studies, is currently ongoing in SGECs from SS and sicca to dissect the link between changes in cell energy metabolism and their acquired pro-inflammatory phenotype. Figure 1. Reference [1]Colafrancesco S, et al. Maladaptive Autophagy in the Pathogenesis of Autoimmune Epithelitis in Sjögren’s Syndrome. Arthritis Rheumatol. 2022;74(4):654-664. Acknowledgements: NIL. Disclosure of Interests None Declared.