Nfil3-independent lineage maintenance and antiviral response of natural killer cells
| العنوان: | Nfil3-independent lineage maintenance and antiviral response of natural killer cells |
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| المؤلفون: | Aimee M. Beaulieu, Eric Vivier, Paul B. Rothman, Masato Kubo, Sharline Madera, Joseph C. Sun, Kimberly S. Schluns, Eliseo F. Castillo, Matthew A. Firth, Georg Gasteiger |
| المصدر: | The Journal of Experimental Medicine |
| بيانات النشر: | Rockefeller University Press, 2013. |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | Muromegalovirus, Cell Survival, Immunology, Cell Separation, Biology, Ligands, Lymphocyte Activation, Article, CD49b, Interferon-gamma, Mice, 03 medical and health sciences, Interleukin 21, 0302 clinical medicine, NK-92, Animals, Homeostasis, Immunology and Allergy, Cell Lineage, 030304 developmental biology, Inflammation, Interleukin-15, 0303 health sciences, Lymphokine-activated killer cell, Janus kinase 3, Flow Cytometry, Natural killer T cell, 3. Good health, Cell biology, Killer Cells, Natural, Mice, Inbred C57BL, Tamoxifen, Basic-Leucine Zipper Transcription Factors, Gene Expression Regulation, Interleukin 12, Myeloid-derived Suppressor Cell, Cytokines, NK Cell Lectin-Like Receptor Subfamily A, Spleen, 030215 immunology |
| الوصف: | Inflammatory cytokines drive NK cell expansion in the absence of the transcription factor Nfil3, and Nfil3 is dispensable for the maintenance and function of mature NK cells. Development of the natural killer (NK) cell lineage is dependent on the transcription factor Nfil3 (or E4BP4), which is thought to act downstream of IL-15 signaling. Nfil3-deficient mice lack NK cells, whereas other lymphocyte lineages (B, T, and NKT cells) remain largely intact. We report the appearance of Ly49H-expressing NK cells in Nfil3−/− mice infected with mouse cytomegalovirus (MCMV) or recombinant viruses expressing the viral m157 glycoprotein. Nfil3−/− NK cells at the peak of antigen-driven expansion were functionally similar to NK cells from infected wild-type mice with respect to IFN-γ production and cytotoxicity, and could comparably produce long-lived memory NK cells that persisted in lymphoid and nonlymphoid tissues for >60 d. We demonstrate that generation and maintenance of NK cell memory is an Nfil3-independent but IL-15–dependent process. Furthermore, specific ablation of Nfil3 in either immature NK cells in the bone marrow or mature peripheral NK cells had no observable effect on NK cell lineage maintenance or homeostasis. Thus, expression of Nfil3 is crucial only early in the development of NK cells, and signals through activating receptors and proinflammatory cytokines during viral infection can bypass the requirement for Nfil3, promoting the proliferation and long-term survival of virus-specific NK cells. |
| تدمد: | 1540-9538 0022-1007 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1f9762c6ff016d836e16eb76d69612f4 https://doi.org/10.1084/jem.20130417 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....1f9762c6ff016d836e16eb76d69612f4 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15409538 00221007 |
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