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Local induction of regulatory T cells prevents inflammatory bone loss in ligature-induced experimental periodontitis in mice
Periodontitis (periodontal disease) is a highly prevalent disease, affecting over 65 million adults in the United States alone. Characterized by an overburden of invasive bacteria, gum inflammation and plaque buildup, over time, these symptoms can result in severe loss of gingival tissue attachment,...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8943171/ https://www.ncbi.nlm.nih.gov/pubmed/35322204 http://dx.doi.org/10.1038/s41598-022-09150-8 |
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author | Greene, Ashlee C. Shehabeldin, Mostafa Gao, Jin Balmert, Stephen C. Ratay, Michelle Sfeir, Charles Little, Steven R. |
author_facet | Greene, Ashlee C. Shehabeldin, Mostafa Gao, Jin Balmert, Stephen C. Ratay, Michelle Sfeir, Charles Little, Steven R. |
author_sort | Greene, Ashlee C. |
collection | PubMed |
description | Periodontitis (periodontal disease) is a highly prevalent disease, affecting over 65 million adults in the United States alone. Characterized by an overburden of invasive bacteria, gum inflammation and plaque buildup, over time, these symptoms can result in severe loss of gingival tissue attachment, bone resorption and even tooth loss. Although current treatments (local antibiotics and scaling and root planing procedures) target the bacterial dysbiosis, they do not address the underlying inflammatory imbalance in the periodontium. In the healthy steady state, the body naturally combats destructive, imbalanced inflammatory responses through regulatory pathways mediated by cells such as regulatory T cells (Tregs). Consequently, we hypothesized that local enrichment of regulatory lymphocytes (Tregs) could restore local, immunological homeostasis and prevent the main outcome of bone loss. Accordingly, we locally delivered a combination of TGFβ, Rapamycin, and IL2 microspheres in a ligature-induced murine periodontitis model. Herein, we have demonstrated this preventative treatment decreases alveolar bone loss, increases the local ratio of Tregs to T effector cells and changes the local microenvironment’s expression of inflammatory and regenerative markers. Ultimately, these Treg-inducing microspheres appear promising as a method to improve periodontitis outcomes and may be able to serve as a platform delivery system to treat other inflammatory diseases. |
format | Online Article Text |
id | pubmed-8943171 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-89431712022-03-28 Local induction of regulatory T cells prevents inflammatory bone loss in ligature-induced experimental periodontitis in mice Greene, Ashlee C. Shehabeldin, Mostafa Gao, Jin Balmert, Stephen C. Ratay, Michelle Sfeir, Charles Little, Steven R. Sci Rep Article Periodontitis (periodontal disease) is a highly prevalent disease, affecting over 65 million adults in the United States alone. Characterized by an overburden of invasive bacteria, gum inflammation and plaque buildup, over time, these symptoms can result in severe loss of gingival tissue attachment, bone resorption and even tooth loss. Although current treatments (local antibiotics and scaling and root planing procedures) target the bacterial dysbiosis, they do not address the underlying inflammatory imbalance in the periodontium. In the healthy steady state, the body naturally combats destructive, imbalanced inflammatory responses through regulatory pathways mediated by cells such as regulatory T cells (Tregs). Consequently, we hypothesized that local enrichment of regulatory lymphocytes (Tregs) could restore local, immunological homeostasis and prevent the main outcome of bone loss. Accordingly, we locally delivered a combination of TGFβ, Rapamycin, and IL2 microspheres in a ligature-induced murine periodontitis model. Herein, we have demonstrated this preventative treatment decreases alveolar bone loss, increases the local ratio of Tregs to T effector cells and changes the local microenvironment’s expression of inflammatory and regenerative markers. Ultimately, these Treg-inducing microspheres appear promising as a method to improve periodontitis outcomes and may be able to serve as a platform delivery system to treat other inflammatory diseases. Nature Publishing Group UK 2022-03-23 /pmc/articles/PMC8943171/ /pubmed/35322204 http://dx.doi.org/10.1038/s41598-022-09150-8 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Greene, Ashlee C. Shehabeldin, Mostafa Gao, Jin Balmert, Stephen C. Ratay, Michelle Sfeir, Charles Little, Steven R. Local induction of regulatory T cells prevents inflammatory bone loss in ligature-induced experimental periodontitis in mice |
title | Local induction of regulatory T cells prevents inflammatory bone loss in ligature-induced experimental periodontitis in mice |
title_full | Local induction of regulatory T cells prevents inflammatory bone loss in ligature-induced experimental periodontitis in mice |
title_fullStr | Local induction of regulatory T cells prevents inflammatory bone loss in ligature-induced experimental periodontitis in mice |
title_full_unstemmed | Local induction of regulatory T cells prevents inflammatory bone loss in ligature-induced experimental periodontitis in mice |
title_short | Local induction of regulatory T cells prevents inflammatory bone loss in ligature-induced experimental periodontitis in mice |
title_sort | local induction of regulatory t cells prevents inflammatory bone loss in ligature-induced experimental periodontitis in mice |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8943171/ https://www.ncbi.nlm.nih.gov/pubmed/35322204 http://dx.doi.org/10.1038/s41598-022-09150-8 |
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