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RESEARCH PRODUCT

SAT0373 Role of Inkt Cells in Patients with Primary Sjogren Syndrome

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Background iNKT cells represent a T cell subset at the bridge between innate and adaptive immunity, playing a role in regulating auto-antibody-producing B cells before their entry into germinal centers. Therefore the absence and/or reduction of iNKT cells seem to increase auto-reactive B cell activation. Primary Sjogren9s syndrome (pSS) is a systemic autoimmune disease in which lymphocyte infiltration and organization in lymphoid structures of inflamed salivary glands occur. Objectives The aim of this study was to investigate the frequency of iNKT in the salivary glands and peripheral blood of patients with pSS and their function by using CD1d/aGalactosylceramide (aGalaCer) tetramers. Methods Flow cytometry analysis of ex vivo frequency of tetramer+ cells, producing IFN-g and IL-17, and quantitative gene expression analysis by real-time PCR for Va24 chain expression was performed on salivary glands and peripheral blood obtained from patients and controls. Flow cytometric analysis and immune fluorescence for autoreactive B lymphocytes and ELISA for anti-SSA detection were also performed. Results A significant expansion of IL-17+- and IFN-γ+-producing iNKT cells, expressing low levels of the chemokine receptors CXCR3, CCR6 and CCR5, was observed in the peripheral blood of pSS patients. In the inflamed salivary glands, iNKT were absent whereas a significant increase of SSA specific B cells occurs. Moreover, co-culture experiments in vitro demonstrate that activated iNKT inhibit autoantibody production by autoreactive B cells from pSS patients. Conclusions An impaired tissue migration of iNKT may lead to the expansion of autoreactive B cells specific for SSA -antigen in salivary glands of patients, suggesting an important role of iNKT in regulating B cells activation in pSS. References Bendelac, A., P. B. Savage, and L. Teyton. The biology of NKT cells. Annu Rev Immunol 2007;25: 297-336. Yang JQ, Wen X, Kim PJ, Singh RR. Invariant NKT cells inhibit autoreactive B cells in a contact- and CD1d-dependentmanner. Invariant NKT cells inhibit autoreactive B cells in a contact- and CD1d-dependent manner. J Immunol. 2011 Feb 1;186(3):1512-20. Wu L, Gabriel CL, Parekh VV, Van Kaer L. Invariant natural killer T cells: innate-like T cells with potent immunomodulatory activities. Tissue Antigens 2009 Jun;73(6):535-45. Disclosure of Interest None declared