THU0280 IL-12 Exacerbates Sjogren's Syndrome through Inducing Lymphocyte Infiltrations into Salivary Glands and Imbalance of Lymphocyte Subsets

Background Primary Sjogren9s syndrome (pSS) is characterized by inflammation of exocrine glands and functional impairment of the salivary and lacrimal glands, accompanied by the disorders of immune system, including increased pro-inflammatory cytokines, decreased anti-inflammatory cytokines, and turbulence of immune cell homeostasis. IL-12 is a pro-inflammatory cytokine relating to autoimmune diseases. However, the role of IL-12 in pSS and the underlying mechanism is still not fully understood. Objectives We aimed to explore the role of IL-12 in the pathogenesis of pSS. Methods Serum IL-12 was detected in pSS patients and healthy controls. The percentages of T cell subsets, B cells and plasma cells in peripheral blood were analyzed. NOD mice (experimental Sjogren9s syndrome model, ESS) were treated with recombinant IL-12 protein, anti IL-12 MAb or same volume of saline, respectively. One week later, the salivary flow rate was detected. Histopathology of submandibular gland, lacrimal gland, lung and kidney were observed by HE staining. Immunochemistry was performed to identify the phenotype of the infiltrated lymphocytes. Flow cytometry was used to detect the proportion of lymphocyte subsets of splenocytes. Results IL-12 levels were significantly higher in pSS patients. Th1, Th17 and Tfh cell percentages were significantly higher in pSS, while Treg percentage was decreased. Th1/Th2 and Th17/Treg ratios were also higher in pSS patients. Besides, plasma cell percentages were also higher in pSS patients. All of the above data suggested the disturbance of both cellular and humoral immune balances in pSS patients. In vivo IL-12 treatment in NOD mice significantly increased salivary gland swollen severity, decreased salivary flow rates, and promoted lymphocyte infiltration in salivary glands, pulmonary interstitium and renal medulla. Immunochemistry staining showed that most of the infiltrated lymphocytes into the organs were CD4+, and a majority of the CD4+ cells were IL17A+, suggesting IL-12 induced Th17 cell infiltrations in multiple organs of NOD mice. On the other hand, anti IL-12 decreased the percentages of Th1, Th17 and Tfh cells, and corrected the imbalance of Th1/Th12 and Th17/Treg ratio. The anti IL-12 also reduced the salivary gland swollen and lymphocyte infiltration, whilst increased salivary flow rates. Conclusions IL-12 deteriorated the pathogenesis of ESS partially by promoting lymphocyte infiltration into the affected organs and disturbance of lymphocyte subsets. Targeting IL-12 may be a potential therapeutic strategy for SS patients. Disclosure of Interest None declared