Artikel
IL-28 as potential therapeutic target for LN and SLE
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Autoren
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Myriam Meineck
- First Department of Medicine, University Medicine of the Johannes Gutenberg University, Mainz
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Andreas Kommer
- First Department of Medicine, University Medicine of the Johannes Gutenberg University, Mainz
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Sabrina Saurin
- First Department of Medicine, University Medicine of the Johannes Gutenberg University, Mainz
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Tamara Möckel
- First Department of Medicine, University Medicine of the Johannes Gutenberg University, Mainz
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Andrea Pautz
- Institute of Pharmacology, University Medicine of the Johannes Gutenberg University, Mainz
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Andreas Schwarting
- First Department of Medicine, University Medicine of the Johannes Gutenberg University, Mainz
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Julia Weinmann-Menke
- First Department of Medicine, University Medicine of the Johannes Gutenberg University, Mainz
| Veröffentlicht: | 18. September 2024 |
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Gliederung
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Introduction: Lupus nephritis (LN) is a common and severe manifestation of the autoimmune disease systemic lupus erythematosus (SLE). Since LN-flares cause irreversible renal damage, and thus may lead to organ failure, there is an urgent need to develop new specific therapeutics. Therefore, we evaluated the disease promoting function of the type III Interferons (IL-28) in murine LN. Moreover, we determined the expression of type III Interferons (IL-28/IL-29) in SLE and LN patients to further explore their role in human autoimmunity.
Methods: The development of LN and systemic autoimmune symptoms were observed in IL-28R Knockout (KO) MRL-Faslpr lupus mice and compared to WT littermates. In an additional experiment MRL-Faslpr mice were treated with a neutralizing anti IL-28 antibody. In LN patients, the type III interferon expression was determined via IHC in renal biopsies. Additionally their expression in blood and urine samples was tested via ELISA. The activation of primary renal tubular epithelial cells (TEC) was examined in vitro.
Results: Both, the knockout of the IL-28 Receptor (IL-28R KO) and treatment with an IL-28 neutralizing antibody resulted in a diminished LN in female MRL-Faslpr mice. In renal biopsies of LN patients the expression of type IL-28, IL-29 and their receptor (IL-28) was observed. Expression of IL-28/29 in urine of LN patients decreased during roughly one year after diagnosis/flare, while the C3c levels increased and the proteinuria tended to decrease. IL-28/29 expression was induced in primary renal TEC after stimulation of RNA sensing receptors and further the expression of pro-inflammatory mediators was observed after stimulation with IL-28 in vitro. The latter suggesting a key disease promoting role of renal tissue cells in the pathology of LN.
Conclusion: Taken our observations in MRL-Faslpr lupus mice, our findings in human LN and our in vitro studies together, we conclude the inhibition of IL-28 signaling should be considered as a therapeutic approach for LN. Moreover, we suggest to further evaluate urine IL-28/29 expression as potential disease activity marker.
Disclosures: Nothing to disclose.
