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      MicroRNAs and immunity in periodontal health and disease

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          Abstract

          MicroRNAs (miRNAs) are critical regulators of the host immune and inflammatory response against bacterial pathogens. In the present review, we discuss target genes, target gene functions, the potential regulatory role of miRNAs in periodontal tissues, and the potential role of miRNAs as biomarkers and therapeutics. In periodontal disease, miRNAs exert control over all aspects of innate and adaptive immunity, including the functions of neutrophils, macrophages, dendritic cells and T and B cells. Previous human studies have highlighted some key miRNAs that are dysregulated in periodontitis patients. In the present study, we mapped the major miRNAs that were altered in our reproducible periodontitis mouse model relative to control animals. The miRNAs that were upregulated as a result of periodontal disease in both human and mouse studies included miR-15a, miR-29b, miR-125a, miR-146a, miR-148/148a and miR-223, whereas miR-92 was downregulated. The association of individual miRNAs with unique aspects of periodontal disease and their stability in gingival crevicular fluid underscores their potential as markers for periodontal disease progression or healthy restitution. Moreover, miRNA therapeutics hold great promise for the future of periodontal therapy because of their ability to modulate the immune response to infection when applied in conjunction with synthetic antagomirs and/or relatively straightforward delivery strategies.

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          Development of monocytes, macrophages, and dendritic cells.

          Monocytes and macrophages are critical effectors and regulators of inflammation and the innate immune response, the immediate arm of the immune system. Dendritic cells initiate and regulate the highly pathogen-specific adaptive immune responses and are central to the development of immunologic memory and tolerance. Recent in vivo experimental approaches in the mouse have unveiled new aspects of the developmental and lineage relationships among these cell populations. Despite this, the origin and differentiation cues for many tissue macrophages, monocytes, and dendritic cell subsets in mice, and the corresponding cell populations in humans, remain to be elucidated.
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            Inflammatory and immune pathways in the pathogenesis of periodontal disease.

            The pathogenesis of periodontitis involves a complex immune/inflammatory cascade that is initiated by the bacteria of the oral biofilm that forms naturally on the teeth. The susceptibility to periodontitis appears to be determined by the host response; specifically, the magnitude of the inflammatory response and the differential activation of immune pathways. The purpose of this review was to delineate our current knowledge of the host response in periodontitis. The role of innate immunity, the failure of acute inflammation to resolve (thus becoming chronic), the cytokine pathways that regulate the activation of acquired immunity and the cells and products of the immune system are considered. New information relating to regulation of both inflammation and the immune response will be reviewed in the context of susceptibility to, and perhaps control of, periodontitis. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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              The kinase Akt1 controls macrophage response to lipopolysaccharide by regulating microRNAs.

              MicroRNAs regulated by lipopolysaccharide (LPS) target genes that contribute to the inflammatory phenotype. Here, we showed that the protein kinase Akt1, which is activated by LPS, positively regulated miRNAs let-7e and miR-181c but negatively regulated miR-155 and miR-125b. In silico analyses and transfection studies revealed that let-7e repressed Toll-like receptor 4 (TLR4), whereas miR-155 repressed SOCS1, two proteins critical for LPS-driven TLR signaling, which regulate endotoxin sensitivity and tolerance. As a result, Akt1(-/-) macrophages exhibited increased responsiveness to LPS in culture and Akt1(-/-) mice did not develop endotoxin tolerance in vivo. Overexpression of let-7e and suppression of miR-155 in Akt1(-/-) macrophages restored sensitivity and tolerance to LPS in culture and in animals. These results indicate that Akt1 regulates the response of macrophages to LPS by controlling miRNA expression.
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                Author and article information

                Contributors
                snares@uic.edu
                diekwisch@tamhsc.edu
                Journal
                Int J Oral Sci
                Int J Oral Sci
                International Journal of Oral Science
                Nature Publishing Group UK (London )
                1674-2818
                2049-3169
                6 August 2018
                6 August 2018
                September 2018
                : 10
                : 3
                : 24
                Affiliations
                [1 ]ISNI 0000 0001 2175 0319, GRID grid.185648.6, Department of Oral Biology, , UIC College of Dentistry, ; Chicago, IL USA
                [2 ]ISNI 0000 0001 2175 0319, GRID grid.185648.6, Department of Periodontics, , UIC College of Dentistry, ; Chicago, IL USA
                [3 ]Department of Periodontics, Texas A&M College of Dentistry, Chicago, IL USA
                Article
                25
                10.1038/s41368-018-0025-y
                6080405
                30078842
                da1197c5-64f3-4cf8-9852-881eacec4956
                © The Author(s) 2018

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 15 February 2018
                : 8 April 2018
                : 11 April 2018
                Categories
                Review Article
                Custom metadata
                © The Author(s) 2018

                Dentistry
                Dentistry

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