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Dendritic cells (DC) are key regulators of T\u00a0cell fate, and biomaterials that recruit and program DC locally can direct T\u00a0cell effector responses. We hypothesized that a biomaterial that recruited and programmed DC toward a tolerogenic phenotype could enrich regulatory T\u00a0cells within periodontal tissue, with the eventual goal of attenuating T\u00a0cell mediated pathology.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The interaction of previously identified factors that could induce tolerance, granulocyte\u2010macrophage colony stimulating factor (GM\u2010CSF) and thymic stromal lymphopoietin (TSLP), with the periodontitis network was confirmed <jats:italic>in silico<\/jats:italic>. The effect of the cytokines on DC migration was explored <jats:italic>in vitro<\/jats:italic> using time\u2010lapse imaging. Finally, regulatory T\u00a0cell enrichment in the dermis and periodontal tissue in response to alginate hydrogels delivering TSLP and GM\u2010CSF was examined<jats:italic>in vivo<\/jats:italic> in mice using immunohistochemistry and live\u2010animal imaging.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The GM\u2010CSF and TSLP interactome connects to the periodontitis network. GM\u2010CSF enhances DC migration <jats:italic>in vitro<\/jats:italic>. An intradermal injection of an alginate hydrogel releasing GM\u2010CSF enhanced DC numbers and the addition of TSLP enriched FOXP3+ regulatory T\u00a0cells locally. Injection of a hydrogel with GM\u2010CSF 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\u201010 in the tissue.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Local biomaterial\u2010mediated delivery of GM\u2010CSF and TSLP can enrich DC and FOXP3+ cells and holds promise for treating the pathologic inflammation of periodontal disease.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jper.19-0411","type":"journal-article","created":{"date-parts":[[2020,3,9]],"date-time":"2020-03-09T17:23:50Z","timestamp":1583774630000},"page":"1475-1485","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Tuning cytokines enriches dendritic cells and regulatory T cells in\u00a0the periodontium"],"prefix":"10.1002","volume":"91","author":[{"given":"R. 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