Ifng

Case study 1: Katelyn J McCann, 2022

Interferon γ (IFNγ) is an essential and pleiotropic activator of human monocytes, but little is known about the changes in cellular metabolism required for IFNγ-induced activation. We sought to elucidate the mechanisms by which IFNγ reprograms monocyte metabolism to support its immunologic activities. IFNγ increased oxygen consumption rates (OCR) in monocytes, indicative of reactive oxygen species generation by both mitochondria and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. Transcriptional profiling revealed that this oxidative phenotype was driven by IFNγ-induced reprogramming of NAD+ metabolism, which is dependent on nicotinamide phosphoribosyltransferase (NAMPT)-mediated NAD+ salvage to generate NADH and NADPH for oxidation by mitochondrial complex I and NADPH oxidase, respectively. Interestingly, inhibition of NAMPT in healthy monocytes completely abrogated the IFNγ-induced oxygen consumption, comparable to levels observed in CGD monocytes. These data identify an IFNγ-induced, NAMPT-dependent, NAD+ salvage pathway that is critical for IFNγ activation of human monocytes.

Fig1. Primary human monocytes were stimulated with media alone, LPS, IFNγ, or LPS plus IFNγ for 24 hours prior to the start of the assay, then ECAR was measured according to the Seahorse Glycolysis Stress Test.

Fig2. IFNγ-induced increases in OCR are unique to type II interferon and not dependent on total mitochondrial mass, glucose uptake, or substrate-specific catabolism.

Case study 2: Julian J Freen-van Heeren, 2020

Long-lasting CD8+ T cell responses are critical in combatting infections and tumors. The pro-inflammatory cytokine IFN-γ is a key effector molecule herein. They researchers recently showed that in murine T cells the production of IFN-γ is tightly regulated through adenylate uridylate-rich elements (AREs) that are located in the 3' untranslated region (UTR) of the Ifng mRNA molecule. Loss of AREs resulted in prolonged cytokine production in activated T cells and boosted anti-tumoral T cell responses. Here, they investigated whether these findings can be translated to primary human T cells.

Utilizing CRISPR-Cas9 technology, they deleted the ARE region from the IFNG 3' UTR in peripheral blood-derived human T cells. Loss of AREs stabilized the IFNG mRNA in T cells and supported a higher proportion of IFN-γ protein-producing T cells. Importantly, combining MART-1 T cell receptor engineering with ARE-Del gene editing showed that this was also true for antigen-specific activation of T cells. MART-1-specific ARE-Del T cells showed higher percentages of IFN-γ producing T cells in response to MART-1 expressing tumor cells.

Fig3. Representative concatenated flow cytometry dot plots of IFN-γ production of control and ARE-Del T cells after removal from stimulus for indicated time points.

Fig4. Representative concatenated flow cytometry dot plots of IFN-γ production of control and ARE-Del T cells after 6, 24, and 48 h of co-culture with MART-1+ and MART-1− tumor cells.

Fig1. Diagram of pathways by which IFNγ regulates cellular NAD+ metabolism. (Katelyn J McCann, 2022)

Fig2. IFN-γ and IL-17 signaling pathways working together, separately. (Hui Dai, 2020)

Ifng involved in several pathways and played different roles in them. We selected most pathways Ifng participated on our site, such as Proteasome, Cytokine-cytokine receptor interaction, HIF- signaling pathway, which may be useful for your reference. Also, other proteins which involved in the same pathway with Ifng were listed below. Creative BioMart supplied nearly all the proteins listed, you can search them on our site.

Ifng has several biochemical functions, for example, cytokine activity, interferon-gamma receptor binding. Some of the functions are cooperated with other proteins, some of the functions could acted by Ifng itself. We selected most functions Ifng had, and list some proteins which have the same functions with Ifng. You can find most of the proteins on our site.

Ifng has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with Ifng here. Most of them are supplied by our site. Hope this information will be useful for your research of Ifng.

IFNGR1; b8_vaccw