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miR-31: a key player in CD8 T-cell exhaustion

Cellular & Molecular Immunology volume 14, pages 954–956 (2017)Cite this article

Over the past decade, miRNAs have emerged as genetic factors that can influence immune functions.1 They act by post-transcriptionally downregulating gene expression either by degrading target mRNAs or by repressing their translation.2 Linking miRNA expression to disease was first accomplished by comparing outcomes in normal animals with those in miR-155 knockout animals.3 Our group also used a viral pathogen to show that knocking out miR-155 resulted in less severe inflammatory lesions caused by herpes simplex virus infection, yet animals without miR-155 became more susceptible to developing viral encephalitis.4, 5 With infectious agents, miRNAs from the agent itself can also influence the outcome of events following infection.6 For example, herpes viruses express many miRNAs, and these, along with several host miRNAs, may influence the type of interaction the virus has with the host.6 These interactions can result in a productive infection, persistence in the form of latency, or, in the case of some herpes viruses, neoplasia.6 MiRNAs may also influence the nature of the inflammatory response to infectious agents that affect, for example, the functional type of lipid mediators produced.7 There have been many mechanistic studies to determine how various miRNAs influence individual immune components that react to infectious agents,1 but the present report of Moffett et al.8 adds an additional chapter to the story. The authors demonstrate that miR-31 production could be a key event in the expression of the immune exhaustion phenotype.

Immune exhaustion has attracted much attention as it appears to explain the failure of the T-cell system to control some cancers and chronic infections.9 As the American public has learned from TV, immune exhaustion can be reversed, and some cancers can now be controlled with commercially available monoclonal antibodies.10 The immune exhaustion concept, as it applies to chronic infections, was first noted by Zinkernagel11 but was popularized by extensive studies of chronic lymphocytic meningitis virus (LCMV), mainly by the Ahmed laboratory.12, 13 The present communication utilizes Ahmed’s LCMV system and makes the novel observation that miR-31 could be responsible for causing the exhaustion phenotype. Such studies may open an additional avenue for pursuing the therapeutic management of exhaustion during chronic infections.

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  1. Barry T Rouse: This work was supported by the National Institutes of Health Grant EY 005093.

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  1. Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, Knoxville, 37996, TN, USA

    Siddheshvar Bhela & Barry T Rouse

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  1. Siddheshvar Bhela
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Correspondence to Barry T Rouse.

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Bhela, S., Rouse, B. miR-31: a key player in CD8 T-cell exhaustion. Cell Mol Immunol 14, 954–956 (2017). https://doi.org/10.1038/cmi.2017.89

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