{"doi":"10.1002/jper.19-0411","title":"Tuning cytokines enriches dendritic cells and regulatory T cells in the periodontium","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.","journal":"Journal of Periodontology","year":2020,"id":77814,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":18,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9505,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":256775,"name":"Catia S. Verbeke","orcid":null,"position":1,"is_corresponding":false},{"id":303710,"name":"Kazuhisa Ouhara","orcid":"0000-0001-6796-884X","position":2,"is_corresponding":false},{"id":355468,"name":"Eduardo A. Silva","orcid":"0000-0003-3173-7622","position":3,"is_corresponding":false},{"id":405946,"name":"Susan X. Hsiong","orcid":null,"position":4,"is_corresponding":false},{"id":303716,"name":"Toshihisa Kawai","orcid":"0000-0003-3310-3818","position":5,"is_corresponding":false},{"id":65893,"name":"David Mooney","orcid":"0000-0001-6299-1194","position":6,"is_corresponding":false},{"id":405037,"name":"R. Warren Sands","orcid":"0000-0002-4410-8860","position":0,"is_corresponding":true}],"reference_count":48,"raw_metadata":null,"created_at":"2026-07-18T21:49:16.197289Z","pmid":"32150760","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}