Tuning cytokines enriches dendritic cells and regulatory T cells in the periodontium. Issue 11 (20th April 2020) - Sands, R. Warren
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 examined in 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.