Year: 2018
Type: article
Abstract: Coordinate control of T cell proliferation, survival, and differentiation are essential for host protection from pathogens and cancer. Long-lived memory cells, whose precursors are formed during the initial immunological insult, provide protection from future encounters and their generation is the goal of many vaccination strategies. microRNAs are key nodes in regulatory networks that shape effective T cell responses through the fine-tuning of thousands of genes. Here, using new compound conditional mutant mice to eliminate miR-15/16 family miRNAs in T cells, we show that miR-15/16 restrict T cell cycle, survival, and memory T cell differentiation. High throughput sequencing of RNA isolated by cross-linking immunoprecipitation of AGO2 combined with gene expression analysis in miR-15/16 deficient T cells indicate that these effects are mediated through the direct inhibition of an extensive network of known and novel target genes within pathways critical to cell cycle, survival, and memory. This study highlights the important role that miRNAs play in shaping the global gene expression program that is required for T cell cycle, survival, and the proper formation of memory cells.
Source: Cell Reports
Authors: John D. Gagnon, Robin Kageyama, Hesham M. Shehata, Marlys S. Fassett, Darryl J. Mar, Eric J. Wigton, Kristina Johansson, Adam J. Litterman, Pamela Odorizzi, Dimitre Simeonov, Brian J. Laidlaw, Marisella Panduro, Sana Patel, Lukas T. Jeker, Margaret E. Feeney, Michael T. McManus, Alexander Marson, Mehrdad Matloubian, Shomyseh Sanjabi, K. Mark Ansel
Institutions: University of California, San Francisco, Gladstone Institutes
Language: English
Topic: T-cell and B-cell Immunology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,620
Funders: National Science Foundation, Burroughs Wellcome Fund, Cancer Research Institute, W. M. Keck Foundation, Leukemia and Lymphoma Society, Gilead Sciences, Sandler Foundation, Parker Institute for Cancer Immunotherapy, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, National Institutes of Health, University of California, San Francisco, National Heart, Lung, and Blood Institute, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, Diabetes Center, University of California, San Francisco
OpenAlex ID: W2969979149