Systemic Lupus erythematosus (SLE) is an autoimmune disease characterised by activated autoreactive lymphocytes and autoantibodies, resulting in tissue damage in multiple organs. An important factor for the disease´s mortality is the development of Lupus nephritis (LN). Type I and III interferons, which are both part of the antiviral defense, have both been associated with the disease´s activity. In sera and urine of SLE patients an enhanced level of IL28/29 was described, but their distinct functional role in the course of disease need to be further investigated.
To determine the role of type I and III interferons during onset and progression of autoimmunity – with focus on the development of LN – the expression of the IFNs and their specific receptors was observed in lupus prone MRL Faslpr mice. These mice develop SLE like symptoms and immunocomplex glomerulonephritis. So far we could confirm the expression of IL28 and it´s receptor by tubular epithelial cells (TEC) in the kidney of MRL Faslpr mice. The overall IL28 mRNA expression increased with disease activity in renal tissue, and a positive correlation to the IFNα and IFNβ expression could be observed. Further the mRNA expression of the IFN receptor mRNA in the spleen accelerated with increasing disease activity.
Furthermore MRL Faslpr mice deficient of the IL28R and/or IFNαR were generated and the progression of autoimmunity and LN was monitored. In preliminary studies with MRL Faslpr IL28R -/- mice, a less extenuated lymphadenopathy and less severe LN at the age of 3 month was observed, compared to their wildtype littermates. Similar observations according the Lymphadenopathy were made in MRL Faslpr IFNαR -/- mice.
Our results suggest a participation of type III IFNs in the development of Lupus nephritis in MRL Faslpr mice. In upcoming experiments the effect of the IL28R knockout will be compared to the effect of the IFNαR knockout and the combined IL28R-IFNαR knockout. The subsequent aim is to transfer the results obtained in the murine model to human SLE and to evaluate IL28 as disease activity marker.
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