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Biomed Res Int. 2017;2017:4927376. doi: 10.1155/2017/4927376. Epub 2017 Nov 26.

Tumor Necrosis Factor-Like Weak Inducer of Apoptosis Activates Type I Interferon Signals in Lupus Nephritis.

Author information

1
Department of Rheumatology and Immunology, The Second Affiliated Hospital of Soochow University, Suzhou, China.
2
Department of Rheumatology and Immunology, The First People's Hospital of Kunshan City, Kunshan, China.

Abstract

Type I interferon (IFN) plays a central role in pathogenesis of systemic lupus erythematosus (SLE); tumor necrosis factor-like weak inducer of apoptosis (TWEAK) has been associated with a pathogenic role in lupus nephritis (LN). Thus we investigated whether TWEAK could induce the activation of type I IFN pathway in LN. We examined this in patient-derived peripheral blood mononuclear cells (PBMCs) as well as MRL/lpr mice, a murine LN model. Relative to the control cohorts, MRL/lpr mice showed severe histological changes, high index levels of renal damage, and elevated expression of type I IFN-inducible genes. After shRNA suppression of TWEAK, we observed that renal damage was significantly attenuated and expression of type I IFN-inducible genes was reduced in MRL/lpr mice. In parallel, siRNA of TWEAK also significantly reduced the expression of type I IFN-inducible genes in PBMCs relative to control transfections. In PBMCs, TWEAK stimulation also led to expression of type I IFN-inducible genes. Our results illustrate a novel regulatory role of TWEAK, in which its activity positively regulates type I IFN pathway in LN based on preclinical models. Our findings suggest TWEAK could act as a critical target in preventing renal damage in patients with LN.

PMID:
29333443
PMCID:
PMC5733219
DOI:
10.1155/2017/4927376
[Indexed for MEDLINE]
Free PMC Article

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