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

AbstractBackgroundPeriodontal 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.MethodsThe 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.ResultsThe 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.ConclusionLocal 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.