IFN-γ, should not be ignored in SLE

Abstract

Systemic lupus erythematosus (SLE) is a typical autoimmune disease with a complex pathogenesis and genetic predisposition. With continued understanding of this disease, it was found that SLE is related to the interferon gene signature. Most studies have emphasized the important role of IFN-α in SLE, but our previous study suggested a nonnegligible role of IFN-γ in SLE. Some scholars previously found that IFN-γ is abnormally elevated as early as before the classification of SLE and before the emergence of autoantibodies and IFN-α. Due to the large overlap between IFN-α and IFN-γ, SLE is mostly characterized by expression of the IFN-α gene after onset. Therefore, the role of IFN-γ in SLE may be underestimated. This article mainly reviews the role of IFN-γ in SLE and focuses on the nonnegligible role of IFN-γ in SLE to gain a more comprehensive understanding of the disease.

Keywords: IFN-γ; autoimmune; biologic therapy; immune cells; systemic lupus erythematosus.

Figure 1

IFN-γ production and canonical signaling pathways. Th1 CD4+ T cells, cytotoxic CD8+ T cells and NK cells and to a lesser extent other cell types, such as dendritic cells (DCs), macrophages and B cells can produce IFN-γ. IFN-γ binds to the IFN-γ receptor (IFNGR) to activate JAK1 and JAK2 leading to the phosphorylation of STAT1 homodimers and binding to the IFN-gamma activation site (GAS) followed by subsequent gene transcribe.

Figure 2

Effects of IFN-γ on several immune cells in the pathogenesis of SLE. IFN-γ affect the function of a variety of immune cells in the pathogenesis of SLE, involving T cell, B cell, macrophage, dendritic cell and et al. The effect of IFN-γ on CD8 cells in SLE is two-sided. IFN-γ can promote the differentiation of naive CD4+ T cells into inflammatory Th1 and Th17 cells, while inhibiting their differentiation into Treg cells and Th2 cells.