miR-15/16 Restrain Memory T Cell Differentiation, Cell Cycle, and Survival.

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

doi:10.1016/j.celrep.2019.07.064

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miR-15/16 Restrain Memory T Cell Differentiation, Cell Cycle, and Survival.

Authors

Gagnon, John D¹
Kageyama, Robin¹
Shehata, Hesham M²
Fassett, Marlys S³
Mar, Darryl J⁴
Wigton, Eric J¹
Johansson, Kristina⁴
Litterman, Adam J⁴
Odorizzi, Pamela⁵
Simeonov, Dimitre⁶
Laidlaw, Brian J⁷
Panduro, Marisella⁴
Patel, Sana⁴
Jeker, Lukas T⁸
Feeney, Margaret E⁵
McManus, Michael T⁹
Marson, Alexander¹⁰
Matloubian, Mehrdad⁵
Sanjabi, Shomyseh¹¹
Ansel, K Mark¹²

¹ Biomedical Sciences Graduate Program, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA; Sandler Asthma Basic Research Ce
² Virology and Immunology, Gladstone Institutes, San Francisco, CA 94158, USA.
³ Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Dermatology, University of California, San Francisco, San Francisco, CA 94143, USA.
⁴ Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA; Sandler Asthma Basic Research Center, University of California, San Francisco, San Francisco, CA 94143, USA.
⁵ Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
⁶ Biomedical Sciences Graduate Program, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA; Diabetes Center, University of C
⁷ Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA.
⁸ Diabetes Center and Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Pathology, University of California, San Francisco, San Francisco, CA 94143, USA.
⁹ Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA; Diabetes Center, University of California, San Francisco, San Francisco, CA 94143, USA.
¹⁰ Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
¹¹ Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA; Virology and Immunology, Gladstone Institutes, San Francisco, CA 94158, USA.
¹² Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA; Sandler Asthma Basic Research Center, University of California, San Francisco, San Francisco, CA 94143, USA. Electronic address: mark.ansel@u

Type

Published Article

Journal

Cell Reports

Publisher

Elsevier

Publication Date

Aug 19, 2019

Volume

28

Issue

8

Identifiers

DOI: 10.1016/j.celrep.2019.07.064

PMID: 31433990

Source

Medline

Keywords

Language

English

License

Unknown

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 (miRNAs) are key nodes in regulatory networks that shape effective T cell responses through the fine-tuning of thousands of genes. Here, using 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 indicates that these effects are mediated through the direct inhibition of an extensive network of target genes within pathways critical to cell cycle, survival, and memory. Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. This record was last updated on 02/02/2021 and may not reflect the most current and accurate biomedical/scientific data available from NLM. The corresponding record at NLM can be accessed at https://www.ncbi.nlm.nih.gov/pubmed/31433990

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