Tuning cytokines enriches dendritic cells and regulatory T cells in the periodontium

R. Warren Sands, Catia S. Verbeke, Kazuhisa Ouhara, Eduardo A. Silva, Susan Hsiong, Toshihisa Kawai, David Mooney

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Background: Periodontal disease results from the pathogenic interactions between the tissue, immune system, and microbiota; however, standard therapy fails to address the cellular mechanism underlying the chronic inflammation. Dendritic cells (DC) are key regulators of T cell fate, and biomaterials that recruit and program DC locally can direct T cell effector responses. We hypothesized that a biomaterial that recruited and programmed DC toward a tolerogenic phenotype could enrich regulatory T cells within periodontal tissue, with the eventual goal of attenuating T cell mediated pathology. Methods: The interaction of previously identified factors that could induce tolerance, granulocyte-macrophage colony stimulating factor (GM-CSF) and thymic stromal lymphopoietin (TSLP), with the periodontitis network was confirmed in silico. The effect of the cytokines on DC migration was explored in vitro using time-lapse imaging. Finally, regulatory T cell enrichment in the dermis and periodontal tissue in response to alginate hydrogels delivering TSLP and GM-CSF was examinedin vivo in mice using immunohistochemistry and live-animal imaging. Results: The GM-CSF and TSLP interactome connects to the periodontitis network. GM-CSF enhances DC migration in vitro. An intradermal injection of an alginate hydrogel releasing GM-CSF enhanced DC numbers and the addition of TSLP enriched FOXP3+ regulatory T cells locally. Injection of a hydrogel with GM-CSF and TSLP into the periodontal tissue in mice increased DC and FOXP3+ cell numbers in the tissue, FOXP3+ cells in the lymph node, and IL-10 in the tissue. Conclusion: Local biomaterial-mediated delivery of GM-CSF and TSLP can enrich DC and FOXP3+ cells and holds promise for treating the pathologic inflammation of periodontal disease.

Original languageEnglish (US)
Pages (from-to)1475-1485
Number of pages11
JournalJournal of Periodontology
Volume91
Issue number11
DOIs
StatePublished - Nov 2020

Keywords

  • adult periodontitis
  • biomaterials
  • dendritic cell
  • immunotherapy
  • regulatory T cells

ASJC Scopus subject areas

  • Periodontics

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