Current prospects of type II interferon γ signaling and autoimmunity

Abstract

Edited by Charles E. SamuelInterferon ␥ (IFN␥) is a pleiotropic protein secreted by immune cells. IFN␥ signals through the IFN␥ receptor, a protein complex that mediates downstream signaling events. Studies into IFN␥ signaling have provided insight into the general concepts of receptor signaling, receptor internalization, regulation of distinct signaling pathways, and transcriptional regulation. Although IFN␥ is the central mediator of the adaptive immune response to pathogens, it has been shown to be involved in several non-infectious physiological processes. This review will provide an introduction into IFN␥ signaling biology and the functional roles of IFN␥ in the autoimmune response.According to the National Institutes of Health, autoimmune diseases (ADs) 3 are one of the top 10 leading causes of death in female children and women in all age groups up to 64 years of age (1). Excess secretion of IFNs has been associated with development of human ADs (2). Interferons (IFNs) comprise a family of proteins classified as type I (IFN-␣, -␤, -⑀, -, and -), type II (IFN-␥, herein IFN␥), and type III (IFN-1-4) that have pleiotropic roles in immunity, cancer biology, and autoimmunity (2). Here, we aim to provide a basic understanding of the functions of the type II IFN␥ and the IFN␥-signaling pathway (hereafter referred to as IFN signaling) in a contextual and timing perspective related to the autoimmune environment and the development of ADs.

IFN‐γ stimulates CpG‐induced IL‐10 production in B cells via p38 and JNK signalling pathways

“…Since IFN‐γ has been described to increase the expression of TLR9 in mouse myeloid DCs and macrophages , to stimulate the proliferation of B cells and to potentially influence mRNA stability , we verified whether the stimulatory effect of IFN‐γ on CpG‐induced IL‐10 could be explained by any of these effects. Therefore, we measured TLR9 expression by intracellular flow cytometry (Supporting Information Fig.…”

Apolipoprotein C-II: New findings related to genetics, biochemistry, and role in triglyceride metabolism

“…For example, in liver, the farnesoid X receptor (known as FXR or NR1H4), which binds bile acids and regulates genes involved in bile acid synthesis and transport, plays a major role in APOC2 gene transcription. In macrophages, however, key transcription factors for the APOC2 gene include the liver X receptor (LXR), whose role is to correct for cellular cholesterol 47, 48 and signal transducer and activator of transcription 1 (STAT1), which mediates cellular responses to interferons and certain cytokines and growth factors 49 . In intestine, ApoC2 gene expression increases with dietary lipids, as might be expected, but recent work in mice has also demonstrated a unique regulatory mechanism involving CD36 sensing of dietary fat 50 .…”

Effects of IFN‐γ on immune cell kinetics during the resolution of acute lung injury

“…The receptor for IFN-γ is comprised of two IFNGR1 chains and two IFNGR2 chains. IFNGR1 is expressed on most cells at moderate levels, while IFNGR2 is expressed at lower levels; however, IFNGR2 expression can be regulated in specific cell types (Bach, Aguet, & Schreiber, 1997;Bernabei et al, 2001;Fenimore, 2016;Green, Young, & Valencia, 2017;Londino et al, 2017). Ifng −/− and Ifngr1 −/− mice develop normally and have a typical immune system, but both genotypes have defects in resistance to some infectious agents, including mycobacterial species, some viruses, and bacteria; conversely, the Ifngr1 −/− mice are more resistant to LPS (Car et al, 1994;Nakamura et al, 2000;Schroder, Hertzog, Ravasi, & Hume, 2004).…”