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346 The contribution of interferon lambda to sle
  1. C Macri1,
  2. ES Pang1,
  3. J Pooley1,
  4. K Radford2 and
  5. M O’Keeffe1
  1. 1Monash University, Biochemistry and Molecular Biology, Clayton, Australia
  2. 2Mater Research-UQ, TRI, Brisbane, Australia

Abstract

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.

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