346 The contribution of interferon lambda to sle

Background and aims Interferon lambda (IFN-λ) is a novel type of interferon produced by dendritic cells (DC). Despite its binding to a different receptor, IFN-λ shares functional similarities with type I IFN (IFN-I) by upregulating the expression of IFN-stimulated genes. The role of IFN-λ in DC biology and in autoimmunity remains unknown. to identify the DC subsets producing IFN-λ. to investigate the role of IFN-λ in DC functions. to investigate the role of IFN-λ in SLE. Methods Mouse and human DC subsets were stimulated ex vivo and the IFN-λ expression was measured. The maturation and the capacity of DC to cross-prime T cells was compared in WT and IFN-λR -/- mice. T cell cross-priming by human DCs was measured ex vivo in the presence of exogenous IFN-λ. Serum levels of IFN-λ was measured in lupus-prone mice and in SLE patients. The phenotype of the blood DC subsets from SLE patients was also characterised. Results Mouse plasmacytoid DC (pDC) and CD8 + DC highly secrete IFN-λ. In humans, the CD141 + DC are the major IFN-λ producers. IFN-λ enhances the capacities of mouse and human DCs to maturate and to cross-prime T cells. High serum levels of IFN-λ were detected in lupus-prone mice and in some SLE patients. SLE patients display increased activation of the IFN-producing DC subsets: the pDCs (producing IFN-I) and the CD141 + DCs (producing IFN-λ). Conclusions IFN-λ is produced by some DC subsets and enhances their functions. Furthermore, IFN-λ is expressed during SLE, suggesting a potential role of the cytokine in the aetiology of SLE.