{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T22:39:29Z","timestamp":1792795169363,"version":"4.5.0"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2024,10,28]],"date-time":"2024-10-28T00:00:00Z","timestamp":1730073600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000072","name":"HHS | NIH | National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["DE029034"],"award-info":[{"award-number":["DE029034"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Chronic inflammatory diseases are a leading global health problem. In many of these diseases, the consistent presence of systemic low-grade inflammation induces tissue damage. This is true in conditions such as diabetes, arthritis, and autoimmune disorders, where an overactive and uncontrolled host immune response is a major driver of immunopathology. Central to this overactive and destructive host response are macrophages, the major phagocytic cells within the innate immune system. These cells exhibit a dual role in both host defense against invading pathogens and promotion of tissue repair during inflammation resolution. Those unique characteristics make macrophages an excellent target for therapeutic interventions in many chronic inflammatory conditions. Using periodontal disease as a model of chronic inflammation, we sought to assess the feasibility of using a controlled drug delivery strategy to target macrophages within the oral cavity. To that end, IL-4 was encapsulated within a biodegradable polymer carrier and locally delivered into the inflamed periodontal tissues. Our data indicate that local sustained delivery of IL-4 decreased inflammatory bone loss and promoted bone gain in the diseased mouse periodontium. Those effects correlated with a shift of local macrophage population toward a prorepair phenotype. Using single-cell RNA sequencing technology, we found that IL-4 delivery reversed several proinflammatory pathways associated with tissue destructive macrophages. Together, our data suggest that sustained delivery of IL-4 may be a viable therapeutic option for chronic diseases characterized by immune-mediated tissue damage.<\/jats:p>","DOI":"10.4049\/jimmunol.2400332","type":"journal-article","created":{"date-parts":[[2024,10,28]],"date-time":"2024-10-28T13:15:52Z","timestamp":1730121352000},"page":"1635-1643","source":"Crossref","is-referenced-by-count":9,"title":["Local Controlled Delivery of IL-4 Decreases Inflammatory Bone Loss in a Murine Model of Periodontal Disease"],"prefix":"10.1093","volume":"213","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2122-4105","authenticated-orcid":false,"given":"Mostafa","family":"Shehabeldin","sequence":"first","affiliation":[{"name":"Center for Craniofacial Regeneration, University of Pittsburgh , Pittsburgh, PA"},{"name":"Department of Periodontics and Preventive Dentistry, School of Dental Medicine, University of Pittsburgh , Pittsburgh, PA"},{"name":"Department of Oral and Craniofacial Sciences, School of Dental Medicine, University of Pittsburgh , Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Kobyra","sequence":"additional","affiliation":[{"name":"Department of Chemical and Petroleum Engineering, University of Pittsburgh , Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yejin","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Oral and Craniofacial Sciences, School of Dental Medicine, University of Pittsburgh , Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6200-4141","authenticated-orcid":false,"given":"Jin","family":"Gao","sequence":"additional","affiliation":[{"name":"Center for Craniofacial Regeneration, University of Pittsburgh , Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Chong","sequence":"additional","affiliation":[{"name":"Center for Craniofacial Regeneration, University of Pittsburgh , Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4053-988X","authenticated-orcid":false,"given":"Tracy","family":"Tabib","sequence":"additional","affiliation":[{"name":"Division of Rheumatology and Clinical Immunology, University of Pittsburgh , Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9398-5034","authenticated-orcid":false,"given":"Robert","family":"Lafyatis","sequence":"additional","affiliation":[{"name":"Division of Rheumatology and Clinical Immunology, University of Pittsburgh , Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven R","family":"Little","sequence":"additional","affiliation":[{"name":"Department of Chemical and Petroleum Engineering, University of Pittsburgh , Pittsburgh, PA"},{"name":"McGowan Institute for Regenerative Medicine, University of Pittsburgh , Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3163-3292","authenticated-orcid":false,"given":"Charles","family":"Sfeir","sequence":"additional","affiliation":[{"name":"Center for Craniofacial Regeneration, University of Pittsburgh , Pittsburgh, PA"},{"name":"Department of Periodontics and Preventive Dentistry, School of Dental Medicine, University of Pittsburgh , Pittsburgh, PA"},{"name":"Department of Oral and Craniofacial Sciences, School of Dental Medicine, University of Pittsburgh , Pittsburgh, PA"},{"name":"McGowan Institute for Regenerative Medicine, University of Pittsburgh , Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,10,28]]},"reference":[{"key":"2025020609300394000_r1","volume-title":"StatPearls.","author":"Pahwa","year":"2023"},{"key":"2025020609300394000_r2","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.it.2013.09.001","article-title":"Immunomicrobial pathogenesis of periodontitis: keystones, pathobionts, and host response","volume":"35","author":"Hajishengallis","year":"2014","journal-title":"Trends Immunol."},{"key":"2025020609300394000_r3","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1016\/j.it.2004.09.015","article-title":"The chemokine system in diverse forms of macrophage activation and polarization","volume":"25","author":"Mantovani","year":"2004","journal-title":"Trends Immunol."},{"key":"2025020609300394000_r4","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1093\/intimm\/dxy054","article-title":"Macrophages in inflammation, repair and regeneration","volume":"30","author":"Oishi","year":"2018","journal-title":"Int. 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