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Review
. 2010:2010:948364.
doi: 10.1155/2010/948364. Epub 2010 Jun 29.

Interferon alpha in systemic lupus erythematosus

Timothy B Niewold  1 , Daniel N Clark, Rafah Salloum, Brian D Poole
Affiliations
Review

Interferon alpha in systemic lupus erythematosus

Timothy B Niewold et al. J Biomed Biotechnol. 2010.

Abstract

The pleiotropic cytokine interferon alpha is involved in multiple aspects of lupus etiology and pathogenesis. Interferon alpha is important under normal circumstances for antiviral responses and immune activation. However, heightened levels of serum interferon alpha and expression of interferon response genes are common in lupus patients. Lupus-associated autoantibodies can drive the production of interferon alpha and heightened levels of interferon interfere with immune regulation. Several genes in the pathways leading to interferon production or signaling are associated with risk for lupus. Clinical and cellular manifestations of excess interferon alpha in lupus combined with the genetic risk factors associated with interferon make this cytokine a rare bridge between genetic risk and phenotypic effects. Interferon alpha influences the clinical picture of lupus and may represent a therapeutic target. This paper provides an overview of the cellular, genetic, and clinical aspects of interferon alpha in lupus.

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Figures

Figure 1
Figure 1
Putative source and effects of interferon alpha in lupus. RNA-containing complexes from apoptotic cells are bound by autoantibodies. These immune complexes are internalized after binding to FC receptors on plasmacytoid dendritic cells and stimulate toll-like receptors in the endosomes. Toll-like receptor ligation drives production of interferon alpha, leading to alteration of T-cell profiles, disruption of regulatory T-cell networks, and alteration of B-cell development.
Figure 2
Figure 2
Multiple genes involved in interferon production and regulation are associated with risk for lupus. Shown are components of the signal transduction pathway from TLR stimulation by nucleic acids to IFN production. Genes that have been associated with risk for lupus are marked (*). IFN: interferon, IRAK: interleukin-1 receptor-associated kinase, IRF: interferon regulatory factor, MyD88: myeloid differentiation primary response gene 88, OPN: osteopontin, pDC: plasmacytoid dendritic cell, TLR: toll-like receptor, TNFAIP3: tumor necrosis factor alpha induced protein 3, TNIP1: TNFAIP3 interacting protein 1, and TRAF6: tumor necrosis factor receptor-associated factor 6.
See this image and copyright information in PMC

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