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miR-451 limits CD4+ T cell proliferative responses to infection in mice

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Abstract

MicroRNAs (miRNAs) are major regulators of cell responses, particularly in stressed cell states and host immune responses. Some miRNAs have a role in pathogen defense, including regulation of immune responses to Plasmodium parasite infection. Using a nonlethal mouse model of blood stage malaria infection, we have found that miR-451−/− mice infected with Plasmodium yoelii XNL cleared infection at a faster rate than did wild-type (WT) mice. MiR-451−/− mice had an increased leukocyte response to infection, with the protective phenotype primarily driven by CD4+ T cells. WT and miR-451−/− CD4+ T cells had similar activation responses, but miR-451−/− CD4+ cells had significantly increased proliferation, both in vitro and in vivo. Myc is a miR-451 target with a central role in cell cycle progression and cell proliferation. CD4+ T cells from miR-451−/− mice had increased postactivation Myc expression. RNA-Seq analysis of CD4+ cells demonstrated over 5000 differentially expressed genes in miR-451−/− mice postinfection, many of which are directly or indirectly Myc regulated. This study demonstrates that miR-451 regulates T cell proliferative responses in part via a Myc-dependent mechanism.

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Acknowledgements

This work is funded by NIH grants to LMC (F31AI108187) and CNM (R01HL124018) and an American Heart Association (13EIA14250023) to CNM. The project was also supported by the following University of Rochester CTSA awards: TL1 RR024135, TL1 TR000096, UL1 RR024160, and UL1 TR000042 from the National Center for Research Resources and the National Center for Advancing Translational Sciences of the National Institutes of Health.

The authors would like to thank Dr. Eric Olson for the miR-451‑/‑ mice. The authors have no financial conflicts.

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Authors and Affiliations

  1. Aab Cardiovascular Research Institute, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY, 14642, USA

    Lesley M. Chapman, Sara K. Ture, David J. Field & Craig N. Morrell

  2. CTSI Translational Biomedical Science, Rochester, NY, USA

    Lesley M. Chapman

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  1. Lesley M. Chapman
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Correspondence to Craig N. Morrell.

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Chapman, L.M., Ture, S.K., Field, D.J. et al. miR-451 limits CD4+ T cell proliferative responses to infection in mice. Immunol Res 65, 828–840 (2017). https://doi.org/10.1007/s12026-017-8919-x

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