IFNG-AS1 Enhances Interferon Gamma Production in Human Natural Killer Cells
Natan Stein,
Orit Berhani,
Dominik Schmiedel,
Alexandra Duev-Cohen,
Einat Seidel,
Inbal Kol,
Pinchas Tsukerman,
Merav Hecht,
Adi Reches,
Moriya Gamliel,
Akram Obeidat,
Yoav Charpak-Amikam,
Rachel Yamin,
Ofer Mandelboim
Affiliations
Natan Stein
The Lautenberg Center for General and Tumor Immunology, Institute for Medical Research Israel-Canada, The Hebrew University Hadassah Medical School, Jerusalem 9112001, Israel
Orit Berhani
The Lautenberg Center for General and Tumor Immunology, Institute for Medical Research Israel-Canada, The Hebrew University Hadassah Medical School, Jerusalem 9112001, Israel
Dominik Schmiedel
The Lautenberg Center for General and Tumor Immunology, Institute for Medical Research Israel-Canada, The Hebrew University Hadassah Medical School, Jerusalem 9112001, Israel
Alexandra Duev-Cohen
The Lautenberg Center for General and Tumor Immunology, Institute for Medical Research Israel-Canada, The Hebrew University Hadassah Medical School, Jerusalem 9112001, Israel
Einat Seidel
The Lautenberg Center for General and Tumor Immunology, Institute for Medical Research Israel-Canada, The Hebrew University Hadassah Medical School, Jerusalem 9112001, Israel
Inbal Kol
The Lautenberg Center for General and Tumor Immunology, Institute for Medical Research Israel-Canada, The Hebrew University Hadassah Medical School, Jerusalem 9112001, Israel
Pinchas Tsukerman
The Lautenberg Center for General and Tumor Immunology, Institute for Medical Research Israel-Canada, The Hebrew University Hadassah Medical School, Jerusalem 9112001, Israel
Merav Hecht
Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, The Hebrew University Hadassah Medical School, Jerusalem 9112001, Israel
Adi Reches
The Lautenberg Center for General and Tumor Immunology, Institute for Medical Research Israel-Canada, The Hebrew University Hadassah Medical School, Jerusalem 9112001, Israel
Moriya Gamliel
The Lautenberg Center for General and Tumor Immunology, Institute for Medical Research Israel-Canada, The Hebrew University Hadassah Medical School, Jerusalem 9112001, Israel
Akram Obeidat
Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112001, Israel
Yoav Charpak-Amikam
The Lautenberg Center for General and Tumor Immunology, Institute for Medical Research Israel-Canada, The Hebrew University Hadassah Medical School, Jerusalem 9112001, Israel
Rachel Yamin
The Lautenberg Center for General and Tumor Immunology, Institute for Medical Research Israel-Canada, The Hebrew University Hadassah Medical School, Jerusalem 9112001, Israel
Ofer Mandelboim
The Lautenberg Center for General and Tumor Immunology, Institute for Medical Research Israel-Canada, The Hebrew University Hadassah Medical School, Jerusalem 9112001, Israel; Corresponding author
Summary: 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. : Molecular Biology; Molecular Mechanism of Gene Regulation; Immunology; Immune Response Subject Areas: Molecular Biology, Molecular Mechanism of Gene Regulation, Immunology, Immune Response