IFNG-AS1 Enhances Interferon Gamma Production in Human Natural Killer Cells

• Published in: iScience Vol. 11; pp. 466 - 473
• Main Authors: Stein, Natan, Berhani, Orit, Schmiedel, Dominik, Duev-Cohen, Alexandra, Seidel, Einat, Kol, Inbal, Tsukerman, Pinchas, Hecht, Merav, Reches, Adi, Gamliel, Moriya, Obeidat, Akram, Charpak-Amikam, Yoav, Yamin, Rachel, Mandelboim, Ofer
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 25.01.2019; Elsevier
• Subjects: Immune Response; Immunology; Molecular Biology; Molecular Mechanism of Gene Regulation; Immunology; Molecular Biology; Molecular Mechanism of Gene Regulation; Immune Response
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2018.12.034

Long, non-coding RNAs (lncRNAs) are involved in the regulation of many cellular processes. The lncRNA IFNG-AS1 was found to strongly influence the responses to several pathogens in mice by increasing interferon gamma (IFNγ) secretion. Studies have looked at IFNG-AS1 in T cells, yet IFNG-AS1 function in natural killer cells (NKs), an important source of IFNγ, remains unknown. Here, we show a previously undescribed sequence of IFNG-AS1 and report that it may be more abundant in cells than previously thought. Using primary human NKs and an NK line with IFNG-AS1 overexpression, we show that IFNG-AS1 is quickly induced upon NK cell activation, and that IFNG-AS1 overexpression leads to increased IFNγ secretion. Taken together, our work expands IFNG-AS1's activity to the innate arm of the type I immune response, helping to explain its notable effect in animal models of disease. [Display omitted] •Natural killer cells (NKs) express a previously undescribed transcript of IFNG-AS1•Upon activation, NKs upregulate IFNG-AS1 along with later IFNγ expression•Overexpression of IFNG-AS1 in an NK line augments IFNγ expression and secretion•IFNG-AS1 influences innate immunity, suggesting a general role in the IFNγ response Molecular Biology; Molecular Mechanism of Gene Regulation; Immunology; Immune Response