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.