{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T04:21:34Z","timestamp":1790310094144,"version":"4.1.0"},"reference-count":330,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T00:00:00Z","timestamp":1787616000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T00:00:00Z","timestamp":1787616000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2023\/15750\u20107"],"award-info":[{"award-number":["2023\/15750\u20107"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Periodontology 2000"],"abstract":"Abstract<\/jats:title>\n \n Objective<\/jats:title>\n Periodontitis, a highly prevalent chronic inflammatory disease, is characterized by the progressive destruction of the tooth\u2010supporting tissues, ultimately causing tooth loss. In recent years, the emerging field of immunometabolism has revealed that immune cell function is tightly regulated by intracellular metabolic pathways that govern cellular activation, differentiation, and effector responses. Therefore, the aim of this review was to synthesize current evidence on the role of immunometabolism in the pathogenesis of periodontitis, with a particular focus on how metabolic reprogramming regulates innate and adaptive immune responses, contributes to inflammatory bone loss, and represents a potential target for host\u2010modulatory therapies.<\/jats:p>\n <\/jats:sec>\n \n Materials and Methods<\/jats:title>\n A comprehensive narrative review of the contemporary literature was conducted to integrate experimental, translational, and clinical evidence on immunometabolic mechanisms involved in periodontitis. The review examines metabolic regulation of innate and adaptive immune cells, the influence of microbial and systemic metabolic signals on periodontal inflammation, and emerging therapeutic strategies targeting immunometabolic pathways.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n Current evidence demonstrates that persistent microbial challenge and inflammatory signaling induce profound metabolic reprogramming of immune cells within the periodontal microenvironment. Activated neutrophils, macrophages, dendritic cells, and lymphocytes undergo coordinated shifts in glycolysis, mitochondrial oxidative phosphorylation, fatty acid oxidation, and amino acid metabolism, which regulate immune cell activation, differentiation, and effector functions. These metabolic adaptations promote the production of reactive oxygen species, pro\u2010inflammatory cytokines, and osteoclastogenic mediators, thereby amplifying inflammation and disrupting osteoimmune mechanisms that maintain bone homeostasis. In addition, microbial\u2010derived metabolites further influence host immune metabolism, reinforcing chronic inflammation and periodontal tissue destruction. Emerging preclinical evidence suggests that pharmacological modulation of key immunometabolic pathways may attenuate inflammation and preserve periodontal tissues.<\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n Immunometabolic reprogramming is a fundamental mechanism linking microbial dysbiosis to dysregulated host immunity and inflammatory bone loss in periodontitis. A better understanding of the metabolic pathways governing immune cell function may provide important mechanistic insights into disease pathogenesis. By integrating insights from (osteo\u2010)immunology and metabolism, this review proposes immunometabolism as a critical determinant of inflammatory bone loss and a fruitful avenue for the development of novel host\u2010modulatory periodontal therapies aimed at restoring immune homeostasis and preventing periodontal tissue destruction.<\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/prd.70073","type":"journal-article","created":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T04:52:41Z","timestamp":1787719961000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Metabolic reprogramming of the immune response in periodontitis"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1110-6233","authenticated-orcid":false,"given":"Rafael Scaf","family":"de Molon","sequence":"first","affiliation":[{"name":"Department of Diagnosis and Surgery, Aracatuba School of Dentistry Sao Paulo State University \u2013 UNESP Ara\u00e7atuba S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Grant","sequence":"additional","affiliation":[{"name":"Periodontal Research Group, Dentistry, School of Health Sciences, College of Medicine and Health University of Birmingham Birmingham UK"},{"name":"Birmingham NIHR Biomedical Research Centre in Inflammation Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2697-7082","authenticated-orcid":false,"given":"Iain","family":"Chapple","sequence":"additional","affiliation":[{"name":"Periodontal Research Group, Dentistry, School of Health Sciences, College of Medicine and Health University of Birmingham Birmingham UK"},{"name":"Birmingham NIHR Biomedical Research Centre in Inflammation Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6071-553X","authenticated-orcid":false,"given":"Joao Paulo","family":"Steffens","sequence":"additional","affiliation":[{"name":"Department of Stomatology Federal University of Paran\u00e1 Curitiba Paran\u00e1 Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,25]]},"reference":[{"issue":"1","key":"e_1_2_15_2_1","first-page":"S173","article-title":"Periodontitis: consensus report of workgroup 2 of the 2017 world workshop on the classification of periodontal and peri\u2010implant diseases and conditions","volume":"89","author":"Papapanou PN","year":"2018","journal-title":"J Periodontol"},{"key":"e_1_2_15_3_1","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2018.01055","article-title":"Changes in nutritional status impact immune cell metabolism and function","volume":"9","author":"Alwarawrah Y","year":"2018","journal-title":"Front Immunol"},{"key":"e_1_2_15_4_1","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1016\/j.chom.2023.02.009","article-title":"Oral 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