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
The Lautenberg Center for General and Tumor Immunology, Institute for Medical Research Israel-Canada, The Hebrew University Hadassah Medical School, Jerusalem 9112001, Israel.
Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, The Hebrew University Hadassah Medical School, Jerusalem 9112001, Israel.
iScience. 2019 Jan 25;11:466-473. doi: 10.1016/j.isci.2018.12.034. Epub 2019 Jan 3.
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.
长链非编码RNA（lncRNAs）参与多种细胞过程的调控。研究发现lncRNA IFNG-AS1通过增加干扰素γ（IFNγ）分泌，强烈影响小鼠对几种病原体的反应。已有研究关注了T细胞中的IFNG-AS1，但IFNG-AS1在作为IFNγ重要来源的自然杀伤细胞（NKs）中的功能仍不清楚。在此，我们展示了IFNG-AS1一个先前未描述的序列，并报告其在细胞中的丰度可能比之前认为的更高。利用原代人NK细胞和IFNG-AS1过表达的NK细胞系，我们发现NK细胞激活后IFNG-AS1会迅速被诱导，且IFNG-AS1过表达会导致IFNγ分泌增加。综上所述，我们的工作将IFNG-AS1的活性扩展到了I型免疫反应的先天免疫分支，有助于解释其在疾病动物模型中的显著作用。
