{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T18:56:34Z","timestamp":1793213794496,"version":"4.5.0"},"reference-count":105,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,11,6]],"date-time":"2024-11-06T00:00:00Z","timestamp":1730851200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Periodontitis is a condition characterized by dysbiosis of microbiota and compromised host immunological responses, resulting in the degradation of periodontal tissues. The aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor, plays a crucial role in the pathogenesis of periodontitis. AHR serves as a pivotal mediator for the adverse impacts of exogenous pollutants on oral health. Research indicates elevated expression of AHR in individuals with periodontitis compared to those without the condition. However, subsequent to the identification of endogenous AHR ligands, researches have elucidated numerous significant advantageous roles associated with AHR activation in bone, immune, and epithelial cells. This review concentrates on the modulation of the AHR pathway and the intricate functions that AHR plays in periodontitis. It discusses the characteristics of AHR ligands, detailing the established physiological functions in maintaining alveolar bone equilibrium, regulating immunity, facilitating interactions between the oral microbiome and host, and providing protection to epithelial tissues, while also exploring its potential roles in systemic disorders related to periodontitis.<\/jats:p>","DOI":"10.3389\/fimmu.2024.1494570","type":"journal-article","created":{"date-parts":[[2024,11,6]],"date-time":"2024-11-06T05:10:21Z","timestamp":1730869821000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["The role of aryl hydrocarbon receptor in the occurrence and development of periodontitis"],"prefix":"10.3389","volume":"15","author":[{"given":"Lingzhi","family":"Wu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiting","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinyu","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Canyu","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuanjiang","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,11,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1111\/jcpe.13506","article-title":"Global, regional, and national burden of severe periodontitis, 1990-2019: An analysis of the Global Burden of Disease Study 2019","volume":"48","author":"Chen","year":"2021","journal-title":"J Clin Periodontol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1111\/prd.12338","article-title":"Prevention and management of periodontal diseases and dental caries in the older adults","volume":"84","author":"Al-Nasser","year":"2020","journal-title":"Periodontol 2000"},{"key":"B3","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1111\/prd.12435","article-title":"Viruses, periodontitis, and comorbidities","volume":"89","author":"Teles","year":"2022","journal-title":"Periodontol 2000"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1080\/21688370.2019.1651158","article-title":"Gingival epithelial barrier: regulation by beneficial and harmful microbes","volume":"7","author":"Takahashi","year":"2019","journal-title":"Tissue Barriers"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-021-00430-8","article-title":"AHR in the intestinal microenvironment: safeguarding barrier function","volume":"18","author":"Stockinger","year":"2021","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"3851","DOI":"10.3390\/ijms19123851","article-title":"The role of the aryl hydrocarbon receptor (AHR) in immune and inflammatory diseases","volume":"19","author":"Neavin","year":"2018","journal-title":"IJMS"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2018.10.010","article-title":"The aryl hydrocarbon receptor: connecting immunity to the microenvironment","volume":"39","author":"Shinde","year":"2018","journal-title":"Trends Immunol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2018.05.003","article-title":"Gut microbiota regulation of tryptophan metabolism in health and disease","volume":"23","author":"Agus","year":"2018","journal-title":"Cell Host Microbe"},{"key":"B9","doi-asserted-by":"crossref","DOI":"10.1016\/j.fob.2014.09.003","article-title":"The activation mechanism of the aryl hydrocarbon receptor (AhR) by molecular chaperone HSP90","volume-title":"FEBS Press","author":"Tsuji","year":"2014"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-019-0125-8","article-title":"The aryl hydrocarbon receptor: an environmental sensor integrating immune responses in health and disease","volume":"19","author":"Rothhammer","year":"2019","journal-title":"Nat Rev Immunol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-020-00585-5","article-title":"The aryl hydrocarbon receptor and the gut\u2013brain axis","volume":"18","author":"Barroso","year":"2021","journal-title":"Cell Mol Immunol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1080\/10408398.2019.1598334","article-title":"Tryptophan (Trp) modulates gut homeostasis via aryl hydrocarbon receptor (AhR)","volume":"60","author":"Sun","year":"2020","journal-title":"Crit Rev Food Sci Nutr"},{"key":"B13","doi-asserted-by":"publisher","first-page":"1846","DOI":"10.1016\/j.cell.2023.03.011","article-title":"Dietary tryptophan metabolite released by intratumoral Lactobacillus reuteri facilitates immune checkpoint inhibitor treatment","volume":"186","author":"Bender","year":"2023","journal-title":"Cell"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw095","article-title":"Alu retrotransposons promote differentiation of human carcinoma cells through the aryl hydrocarbon receptor","volume":"44","author":"Morales-Hern\u00e1ndez","year":"2016","journal-title":"Nucleic Acids Res"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1501727","article-title":"Dietary indoles suppress delayed-type hypersensitivity by inducing a switch from proinflammatory Th17 cells to anti-inflammatory regulatory T cells through regulation of MicroRNA","volume":"196","author":"Singh","year":"2016","journal-title":"J Immunol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2008.08.034","article-title":"AhR acts as an E3 ubiquitin ligase to modulate steroid receptor functions","volume":"77","author":"Ohtake","year":"2009","journal-title":"Biochem Pharmacol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1038\/nature13323","article-title":"Aryl hydrocarbon receptor control of a disease tolerance defense pathway","volume":"511","author":"Bessede","year":"2014","journal-title":"Nature"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)75608-7","article-title":"Dioxin","volume":"353","author":"Gough","year":"1999","journal-title":"Lancet"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2000047117","article-title":"Microbial tryptophan metabolites regulate gut barrier function via the aryl hydrocarbon receptor","volume":"117","author":"Scott","year":"2020","journal-title":"Proc Natl Acad Sci U.S.A"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1177\/0022034515606045","article-title":"Oral microbiome metabolism: from \u201cWho are they?\u201d to \u201cWhat are they doing","volume":"94","author":"Takahashi","year":"2015","journal-title":"J Dent Res"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1126\/science.aah5825","article-title":"Lactobacillus reuteri induces gut intraepithelial CD4+CD8\u03b1\u03b1+ T cells","volume":"357","author":"Cervantes-Barragan","year":"2017","journal-title":"Science"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1002\/mnfr.201200594","article-title":"Major phenylpropanoid-derived metabolites in the human gut can arise from microbial fermentation of protein","volume":"57","author":"Russell","year":"2013","journal-title":"Mol Nutr Food Res"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1128\/aem.38.3.544-546.1979","article-title":"Indole-3-lactic acid as a tryptophan metabolite produced by Bifidobacterium spp","volume":"38","author":"Aragozzini","year":"1979","journal-title":"Appl Environ Microbiol"},{"key":"B24","doi-asserted-by":"publisher","first-page":"837","DOI":"10.1016\/j.cmet.2020.03.003","article-title":"Microbiota-derived metabolites suppress arthritis by amplifying aryl-hydrocarbon receptor activation in regulatory B cells","volume":"31","author":"Rosser","year":"2020","journal-title":"Cell Metab"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1007\/s12016-020-08789-3","article-title":"The aryl hydrocarbon receptor (AHR) as a potential target for the control of intestinal inflammation: insights from an immune and bacteria sensor receptor","volume":"59","author":"Pernomian","year":"2020","journal-title":"Clin Rev Allergy Immunol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1172\/JCI170753","article-title":"Aryl hydrocarbon receptor sulfenylation promotes glycogenolysis and rescues cancer chemoresistance","volume":"133","author":"Zhou","year":"2023","journal-title":"J Clin Invest"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/j.cotox.2017.01.007","article-title":"Is chronic AhR activation by rapidly metabolized ligands safe for the treatment of immune-mediated diseases","volume":"2","author":"Ehrlich","year":"2017","journal-title":"Curr Opin Toxicol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M808321200","article-title":"The suggested physiologic aryl hydrocarbon receptor activator and cytochrome P4501 substrate 6-formylindolo[3,2-b]carbazole is present in humans","volume":"284","author":"Wincent","year":"2009","journal-title":"J Biol Chem"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1021\/jf020415z","article-title":"Metabolism of polychlorinated dibenzo-p-dioxins (PCDDs) by human cytochrome P450-dependent monooxygenase systems","volume":"50","author":"Inouye","year":"2002","journal-title":"J Agric Food Chem"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1124\/mol.65.5.1225","article-title":"Oral exposure to benzo[a]pyrene in the mouse: detoxication by inducible cytochrome P450 is more important than metabolic activation","volume":"65","author":"Uno","year":"2004","journal-title":"Mol Pharmacol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1177\/00220345460250040601","article-title":"Chemical studies in periodontal disease III: putrefaction of salivary proteins","volume":"25","author":"Berg","year":"1946","journal-title":"J Dent Res"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.3760\/cma.j.cn112144-20230318-00095","article-title":"Effects of the kynurenine pathway on the osteogenic differentiation of periodontal ligament stem cells","volume":"58","author":"Wang","year":"2023","journal-title":"Zhonghua Kou Qiang Yi Xue Za Zhi"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1007\/s10753-023-01948-6","article-title":"High-throughput combined analysis of saliva microbiota and metabolomic profile in chinese periodontitis patients: A pilot study","volume":"47","author":"Ding","year":"2023","journal-title":"Inflammation"},{"key":"B34","doi-asserted-by":"publisher","first-page":"14927","DOI":"10.1038\/s41598-021-94470-4","article-title":"Roles for B[a]P and FICZ in subchondral bone metabolism and experimental temporomandibular joint osteoarthritis via the AhR\/Cyp1a1 signaling axis","volume":"11","author":"Yoshikawa","year":"2021","journal-title":"Sci Rep"},{"key":"B35","doi-asserted-by":"publisher","first-page":"7669","DOI":"10.3390\/ijms22147669","article-title":"Cigarette smoke stimulates SARS-coV-2 internalization by activating ahR and increasing ACE2 expression in human gingival epithelial cells","volume":"22","author":"Almeida-da-Silva","year":"2021","journal-title":"IJMS"},{"key":"B36","doi-asserted-by":"publisher","first-page":"893","DOI":"10.1111\/jre.12461","article-title":"Increased levels of the T-helper 22-associated cytokine (interleukin-22) and transcription factor (aryl hydrocarbon receptor) in patients with periodontitis are associated with osteoclast resorptive activity and severity of the disease","volume":"52","author":"D\u00edaz-Z\u00fa\u00f1iga","year":"2017","journal-title":"J Periodont Res"},{"key":"B37","doi-asserted-by":"publisher","first-page":"7434","DOI":"10.3390\/ijerph19127434","article-title":"Transcription factor ahR, cytokines IL-6 and IL-22 in subjects with and without peri-implantitis: A case control-study","volume":"19","author":"Martins","year":"2022","journal-title":"Int J Environ Res Public Health"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1111\/jre.12654","article-title":"IL -22\u2013expressing CD 4 + AhR + T lymphocytes are associated with RANKL -mediated alveolar bone resorption during experimental periodontitis","volume":"54","author":"Monasterio","year":"2019","journal-title":"J Periodont Res"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1111\/jcpe.13166","article-title":"Protective roles of FICZ and aryl hydrocarbon receptor axis on alveolar bone loss and inflammation in experimental periodontitis","volume":"46","author":"Huang","year":"2019","journal-title":"J Clin Periodontol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.2c00956","article-title":"The highly potent ahR agonist picoberin modulates hh-dependent osteoblast differentiation","volume":"65","author":"Flegel","year":"2022","journal-title":"J Med Chem"},{"key":"B41","doi-asserted-by":"publisher","first-page":"11265","DOI":"10.3390\/ijms222011265","article-title":"Toxic effects of indoxyl sulfate on osteoclastogenesis and osteoblastogenesis","volume":"22","author":"Shyu","year":"2021","journal-title":"Int J Mol Sci"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2014.08.025","article-title":"The aryl hydrocarbon receptor suppresses osteoblast proliferation and differentiation through the activation of the ERK signaling pathway","volume":"280","author":"Yu","year":"2014","journal-title":"Toxicol Appl Pharmacol"},{"key":"B43","doi-asserted-by":"publisher","first-page":"225","DOI":"10.3390\/ijms19010225","article-title":"Aryl hydrocarbon receptor antagonists mitigate the effects of dioxin on critical cellular functions in differentiating human osteoblast-like cells","volume":"19","author":"Yun","year":"2018","journal-title":"Int J Mol Sci"},{"key":"B44","doi-asserted-by":"publisher","first-page":"2600","DOI":"10.3390\/molecules23102600","article-title":"Isopsoralen enhanced osteogenesis by targeting ahR\/ER\u03b1","volume":"23","author":"Ge","year":"2018","journal-title":"Molecules"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2005.04.028","article-title":"Inhibition of osteoclast differentiation by polycyclic aryl hydrocarbons is dependent on cell density and RANKL concentration","volume":"70","author":"Voronov","year":"2005","journal-title":"Biochem Pharmacol"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2009.02.019","article-title":"Dioxins interfere with differentiation of osteoblasts and osteoclasts","volume":"44","author":"Korkalainen","year":"2009","journal-title":"Bone"},{"key":"B47","doi-asserted-by":"publisher","first-page":"3486","DOI":"10.3390\/ijms21103486","article-title":"Concentration and duration of indoxyl sulfate exposure affects osteoclastogenesis by regulating NFATc1 via aryl hydrocarbon receptor","volume":"21","author":"Liu","year":"2020","journal-title":"Int J Mol Sci"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1220919110","article-title":"Smoke carcinogens cause bone loss through the aryl hydrocarbon receptor and induction of Cyp1 enzymes","volume":"110","author":"Iqbal","year":"2013","journal-title":"Proc Natl Acad Sci"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1111\/jre.2016.51.issue-6","article-title":"Benzo[a]pyrene\/aryl hydrocarbon receptor signaling inhibits osteoblastic differentiation and collagen synthesis of human periodontal ligament cells","volume":"51","author":"Monnouchi","year":"2016","journal-title":"J Periodontal Res"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.v113.10","article-title":"Alternation of extracellular matrix remodeling and apoptosis by activation of the aryl hydrocarbon receptor pathway in human periodontal ligament cells","volume":"113","author":"Tomokiyo","year":"2012","journal-title":"J Cell Biochem"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1677\/joe.0.1670183","article-title":"Inhibition of dioxin effects on bone formation in vitro by a newly described aryl hydrocarbon receptor antagonist, resveratrol","volume":"167","author":"Singh","year":"2000","journal-title":"J Endocrinol"},{"key":"B52","doi-asserted-by":"publisher","first-page":"101617","DOI":"10.1016\/j.molmet.2022.101617","article-title":"Indoleamine 2,3-dioxygenase mediates the therapeutic effects of adipose-derived stromal\/stem cells in experimental periodontitis by modulating macrophages through the kynurenine-AhR-NRF2 pathway","volume":"66","author":"Li","year":"2022","journal-title":"Mol Metab"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1590\/1678-7757-2018-0713","article-title":"Effects of 1,25-dihydroxyvitamin D3 on experimental periodontitis and AhR\/NF-\u03baB\/NLRP3 inflammasome pathway in a mouse model","volume":"27","author":"Li","year":"2019","journal-title":"J Appl Oral Sci"},{"key":"B54","doi-asserted-by":"publisher","first-page":"7931","DOI":"10.3390\/ijms21217931","article-title":"Kynurenine promotes RANKL-induced osteoclastogenesis in vitro by activating the aryl hydrocarbon receptor pathway","volume":"21","author":"Eisa","year":"2020","journal-title":"Int J Mol Sci"},{"key":"B55","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1186\/s10020-023-00614-9","article-title":"Indole-3-propionic acid alleviates chondrocytes inflammation and osteoarthritis via the AhR\/NF-\u03baB axis","volume":"29","author":"Zhuang","year":"","journal-title":"Mol Med"},{"key":"B56","doi-asserted-by":"publisher","first-page":"109314","DOI":"10.1016\/j.intimp.2022.109314","article-title":"Indole-3-aldehyde alleviates chondrocytes inflammation through the AhR-NF-\u03baB signalling pathway","volume":"113","author":"Zhuang","year":"2022","journal-title":"Int Immunopharmacology"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbiomolbio.2017.12.005","article-title":"The role of aryl hydrocarbon receptor in bone remodeling","volume":"134","author":"Yu","year":"2018","journal-title":"Prog Biophys Mol Biol"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfy225","article-title":"Evidence for aryl hydrocarbon receptor-mediated inhibition of osteoblast differentiation in human mesenchymal stem cells","volume":"167","author":"Watson","year":"2019","journal-title":"Toxicol Sci"},{"key":"B59","doi-asserted-by":"publisher","first-page":"3394","DOI":"10.3390\/ijms20143394","article-title":"Th17 cells and the IL-23\/IL-17 axis in the pathogenesis of periodontitis and immune-mediated inflammatory diseases","volume":"20","author":"Bunte","year":"2019","journal-title":"Int J Mol Sci"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.09.082","article-title":"AHR activation is protective against colitis driven by T cells in humanized mice","volume":"17","author":"Goettel","year":"2016","journal-title":"Cell Rep"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1038\/nature14452","article-title":"TH17 cells transdifferentiate into regulatory T cells during resolution of inflammation","volume":"523","author":"Gagliani","year":"2015","journal-title":"Nature"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1915","article-title":"Activation of the aryl hydrocarbon receptor induces human type 1 regulatory T cell\u2013like and Foxp3+ regulatory T cells","volume":"11","author":"Gandhi","year":"2010","journal-title":"Nat Immunol"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1126\/science.1191536","article-title":"Aryl hydrocarbon receptor antagonists promote the expansion of human hematopoietic stem cells","volume":"329","author":"Boitano","year":"2010","journal-title":"Science"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1009201107","article-title":"An endogenous aryl hydrocarbon receptor ligand acts on dendritic cells and T cells to suppress experimental autoimmune encephalomyelitis","volume":"107","author":"Quintana","year":"2010","journal-title":"Proc Natl Acad Sci"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1111\/cpr.13364","article-title":"Porphyromonas gingivalis infection promotes inflammation via inhibition of the AhR signalling pathway in periodontitis","volume":"56","author":"Hao","year":"2022","journal-title":"Cell Prolif"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1038\/nature13684","article-title":"AhR sensing of bacterial pigments regulates antibacterial defence","volume":"512","author":"Moura-Alves","year":"2014","journal-title":"Nature"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2309032120","article-title":"Bacterial indole-3-lactic acid affects epithelium-macrophage crosstalk to regulate intestinal homeostasis","volume":"120","author":"Yu","year":"2023","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B68","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.immuni.2017.12.012","article-title":"Regulation of the immune response by the aryl hydrocarbon receptor","volume":"48","author":"Guti\u00e9rrez-V\u00e1zquez","year":"2018","journal-title":"Immunity"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-022-01196-8","article-title":"Multi-omics analyses of airway host\u2013microbe interactions in chronic obstructive pulmonary disease identify potential therapeutic interventions","volume":"7","author":"Yan","year":"2022","journal-title":"Nat Microbiol"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2021-003725","article-title":"Optimizing therapeutic outcomes of immune checkpoint blockade by a microbial tryptophan metabolite","volume":"10","author":"Renga","year":"2022","journal-title":"J Immunother Cancer"},{"key":"B71","doi-asserted-by":"publisher","first-page":"111653","DOI":"10.1016\/j.foodres.2022.111653","article-title":"Interactions between polysaccharides and gut microbiota: A metabolomic and microbial review","volume":"160","author":"Zhang","year":"2022","journal-title":"Food Res Int"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2015.00085","article-title":"Interleukin-22 signaling in the regulation of intestinal health and disease","volume":"3","author":"Parks","year":"2015","journal-title":"Front Cell Dev Biol"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1038\/nm1720","article-title":"Interleukin-22 mediates early host defense against attaching and effacing bacterial pathogens","volume":"14","author":"Zheng","year":"2008","journal-title":"Nat Med"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-0764-0","article-title":"Interleukin-22-mediated host glycosylation prevents Clostridioides difficile infection by modulating the metabolic activity of the gut microbiota","volume":"26","author":"Nagao-Kitamoto","year":"2020","journal-title":"Nat Med"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1002\/JPER.20-0262","article-title":"Maintaining barrier function of infected gingival epithelial cells by inhibition of DNA methylation","volume":"91","author":"Barros","year":"2020","journal-title":"J Periodontology"},{"key":"B76","doi-asserted-by":"publisher","first-page":"3176","DOI":"10.3390\/cells10113176","article-title":"Role of AHR ligands in skin homeostasis and cutaneous inflammation","volume":"10","author":"Fern\u00e1ndez-Gallego","year":"2021","journal-title":"Cells"},{"key":"B77","doi-asserted-by":"publisher","first-page":"1235","DOI":"10.1016\/j.chom.2021.05.011","article-title":"Commensal microbiota regulates skin barrier function and repair via signaling through the aryl hydrocarbon receptor","volume":"29","author":"Uberoi","year":"2021","journal-title":"Cell Host Microbe"},{"key":"B78","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1038\/s41467-018-07859-7","article-title":"Enhancement of the gut barrier integrity by a microbial metabolite through the Nrf2 pathway","volume":"10","author":"Singh","year":"2019","journal-title":"Nat Commun"},{"key":"B79","doi-asserted-by":"publisher","first-page":"69","DOI":"10.7150\/ijbs.22259","article-title":"Aryl hydrocarbon receptor activation modulates intestinal epithelial barrier function by maintaining tight junction integrity","volume":"14","author":"Yu","year":"2018","journal-title":"Int J Biol Sci"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06508-4","article-title":"Endothelial sensing of AHR ligands regulates intestinal homeostasis","volume":"621","author":"Wiggins","year":"2023","journal-title":"Nature"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1097\/SHK.0000000000000594","article-title":"Aryl hydrocarbon receptor activation in intestinal obstruction ameliorates intestinal barrier dysfunction via suppression of MLCK-MLC phosphorylation pathway","volume":"46","author":"Han","year":"2016","journal-title":"Shock"},{"key":"B82","doi-asserted-by":"publisher","first-page":"110166","DOI":"10.1016\/j.intimp.2023.110166","article-title":"Spermidine protects intestinal mucosal barrier function in mice colitis via the AhR\/Nrf2 and AhR\/STAT3 signaling pathways","volume":"119","author":"Yan","year":"2023","journal-title":"Int Immunopharmacol"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(03)12521-4","article-title":"Alzheimer\u2019s disease and angiogenesis","volume":"361","author":"Vagnucci","year":"2003","journal-title":"Lancet"},{"key":"B84","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/j.bbi.2019.07.002","article-title":"Systemic inflammation linking chronic periodontitis to cognitive decline","volume":"81","author":"Wang","year":"2019","journal-title":"Brain Behav Immun"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2007.08.004","article-title":"Inflammation and Alzheimer\u2019s disease: possible role of periodontal diseases","volume":"4","author":"Kamer","year":"2008","journal-title":"Alzheimers Dement"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.1111\/jgs.2019.67.issue-6","article-title":"Association of chronic periodontitis on alzheimer\u2019s disease or vascular dementia","volume":"67","author":"Choi","year":"2019","journal-title":"J Am Geriatr Soc"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.1016\/j.xinn.2023.100547","article-title":"Restoring periodontal tissue homoeostasis prevents cognitive decline by reducing the number of Serpina3nhigh astrocytes in the hippocampus","volume":"5","author":"Shen","year":"2024","journal-title":"Innovation"},{"key":"B88","doi-asserted-by":"publisher","first-page":"228","DOI":"10.3390\/nu13010228","article-title":"Altered gut microbial metabolites in amnestic mild cognitive impairment and alzheimer\u2019s disease: signals in host-microbe interplay","volume":"13","author":"Wu","year":"2021","journal-title":"Nutrients"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-023-02289-5","article-title":"Activation of aryl hydrocarbon receptor (AhR) in Alzheimer\u2019s disease: role of tryptophan metabolites generated by gut host-microbiota","volume":"101","author":"Salminen","year":"2023","journal-title":"J Mol Med (Berl)"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2022857118","article-title":"Whole-blood metabolomics of dementia patients reveal classes of disease-linked metabolites","volume":"118","author":"Teruya","year":"2021","journal-title":"Proc Natl Acad Sci"},{"key":"B91","doi-asserted-by":"publisher","first-page":"2126272","DOI":"10.1080\/19490976.2022.2126272","article-title":"Periodontitis-related salivary microbiota aggravates Alzheimer\u2019s disease via gut-brain axis crosstalk","volume":"14","author":"Lu","year":"2022","journal-title":"Gut Microbes"},{"key":"B92","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aau3333","article-title":"Porphyromonas gingivalis in Alzheimer\u2019s disease brains: Evidence for disease causation and treatment with small-molecule inhibitors","volume":"5","author":"Dominy","year":"2019","journal-title":"Sci Adv"},{"key":"B93","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1097\/WCO.0000000000000797","article-title":"Linking mechanisms of periodontitis to Alzheimer\u2019s disease","volume":"33","author":"Sadrameli","year":"2020","journal-title":"Curr Opin Neurology"},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.7150\/thno.61601","article-title":"Activating AhR alleviates cognitive deficits of Alzheimer\u2019s disease model mice by upregulating endogenous A\u03b2 catabolic enzyme Neprilysin","volume":"11","author":"Qian","year":"2021","journal-title":"Theranostics"},{"key":"B95","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2009.28","article-title":"Periodontitis in systemic rheumatic diseases","volume":"5","author":"de Pablo","year":"2009","journal-title":"Nat Rev Rheumatol"},{"key":"B96","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2022.962969","article-title":"Pathomechanisms of bone loss in rheumatoid arthritis","volume":"9","author":"Sakthiswary","year":"2022","journal-title":"Front Med (Lausanne)"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.1002\/JLB.3MA0121-045R","article-title":"Porphyromonas gingivalis induces periodontitis, causes immune imbalance, and promotes rheumatoid arthritis","volume":"110","author":"Zhou","year":"2021","journal-title":"J leukocyte Biol"},{"key":"B98","doi-asserted-by":"publisher","DOI":"10.1038\/s41397-021-00238-4","article-title":"AHR-dependent genes and response to MTX therapy in rheumatoid arthritis patients","volume":"21","author":"Wajda","year":"2021","journal-title":"Pharmacogenomics J"},{"key":"B99","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1722124115","article-title":"Shared epitope-aryl hydrocarbon receptor crosstalk underlies the mechanism of gene-environment interaction in autoimmune arthritis","volume":"115","author":"Fu","year":"2018","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B100","doi-asserted-by":"publisher","first-page":"1280","DOI":"10.3390\/biom10091280","article-title":"Amino acid metabolism in rheumatoid arthritis: friend or foe","volume":"10","author":"Panfili","year":"2020","journal-title":"Biomolecules"},{"key":"B101","doi-asserted-by":"publisher","DOI":"10.1016\/j.scib.2023.06.027","article-title":"Sinomenine ameliorates rheumatoid arthritis by modulating tryptophan metabolism and activating aryl hydrocarbon receptor via gut microbiota regulation","volume":"68","author":"Jiang","year":"2023","journal-title":"Sci Bull (Beijing)"},{"key":"B102","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2011.106","article-title":"Diabetes mellitus and periodontitis: a tale of two common interrelated diseases","volume":"7","author":"Lalla","year":"2011","journal-title":"Nat Rev Endocrinol"},{"key":"B103","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/91.9.779","article-title":"Cancer, heart disease, and diabetes in workers exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin","volume":"91","author":"Steenland","year":"1999","journal-title":"J Natl Cancer Inst"},{"key":"B104","doi-asserted-by":"publisher","DOI":"10.1038\/npjbiofilms.2016.14","article-title":"Bidirectional communication between the Aryl hydrocarbon Receptor (AhR) and the microbiome tunes host metabolism","volume":"2","author":"Korecka","year":"2016","journal-title":"NPJ biofilms microbiomes"},{"key":"B105","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1186\/s11658-022-00397-7","article-title":"Insight into the physiological and pathological roles of the aryl hydrocarbon receptor pathway in glucose homeostasis, insulin resistance, and diabetes development","volume":"27","author":"Sayed","year":"2022","journal-title":"Cell Mol Biol Lett"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2024.1494570\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,6]],"date-time":"2024-11-06T05:10:29Z","timestamp":1730869829000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2024.1494570\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,6]]},"references-count":105,"alternative-id":["10.3389\/fimmu.2024.1494570"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2024.1494570","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,6]]},"article-number":"1494570"}}