SAT0016 Il-12 suppress tr1 cells in the sjÖgren’s syndrome

Background Sjogren’s syndrome (SS) is a systemic autoimmune disorder characterised by lymphocytic infiltration of salivary and lachrymal gland leading to dry mouth and eye dryness progressively. It is known that pro-inflammatory cytokines and dysfunction of immune cells play an important role in the pathogenesis of SS. The regulatory T cell type 1 (Tr1) cells have strong immunosuppressive properties and alleviate inflammatory diseases. However, the role of Tr1 cells in SS and the underlying mechanism is still not fully understood. Objectives This study aims to determine the association of Tr1 cells with the disease pathogenesis using a murine model of SS and patients with SS. Methods The frequencies of Tr1 cells in blood, cervical lymph nodes and their association with disease severity were determined in SS mice. Since proinflammatory interleukine 12 (IL-12) have the ability to regulate the generation of Tr1 cells, the serum IL-12 and its association with disease severity and Tr1 cells were also examined. The involvement of IL-12 and a Tr1 response was examined by recombinant IL-12 treatment or anti-IL-12 antibody neutralisation in SS mice and monitored for SS development. The mouse naive CD4 +cells were treated with IL-12 under Tr1 polarising condition. The frequency of Tr1 cells and their association with IL-12 and disease activity were verified in SS patients. Results Tr1 cells significantly decreased in SS mice and patients with SS, which correlated negatively with disease activity and proinflammatory IL-12 (figure 1A,B). IL-12 suppressed Tr1 cell polarisation ex vivo. SS mice treated with the recombinant IL-12 displayed significantly lower saliva flow rates and pronounced inflammation and tissue damage in salivary glands, accompanying with reduction of Tr1 cells. However, anti-IL-12 antibody treatment profoundly increased the numbers of Tr1 cells and ameliorated the reduction in salivary secretion and inflammation and tissue damage in salivary glands in SS mice (figure 1C). Conclusions Our findings indicate that proinflammatory IL-12 with its capacity to inhibit Tr1 cell generation may be a critical pathogenic factor in Sjogren’s syndrome. Targeting IL-12 and Tr1 cells may be a novel therapeutic strategy for the treatment of Sjogren’s syndrome. Disclosure of Interest None declared