title: On-going Mechanical Damage from Mastication Drives Homeostatic Th17 Cell Responses at the Oral Barrier.
abstract: Immuno-surveillance networks operating at barrier sites are tuned by local tissue cues to ensure effective immunity. Site-specific commensal bacteria provide key signals ensuring host defense in the skin and gut. However, how the oral microbiome and tissue-specific signals balance immunity and regulation at the gingiva, a key oral barrier, remains minimally explored. In contrast to the skin and gut, we demonstrate that gingiva-resident T helper 17 (Th17) cells developed via a commensal colonization-independent mechanism. Accumulation of Th17 cells at the gingiva was driven in response to the physiological barrier damage that occurs during mastication. Physiological mechanical damage, via induction of interleukin 6 (IL-6) from epithelial cells, tailored effector T cell function, promoting increases in gingival Th17 cell numbers. These data highlight that diverse tissue-specific mechanisms govern education of Th17 cell responses and demonstrate that mechanical damage helps define the immune tone of this important oral barrier.
authors.affiliation: Oral Immunity and Inflammation Unit, NIDCR, NIH, Bethesda, MD 20892, USA.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Dutzan
authors.affiliation: Oral Immunity and Inflammation Unit, NIDCR, NIH, Bethesda, MD 20892, USA.
authors.forename: Loreto
authors.initials: L
authors.lastname: Abusleme
authors.affiliation: Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PT, UK; Manchester Collaborative Centre for Inflammation Research (MCCIR), University of Manchester, Manchester M13 9NT, UK.
authors.forename: Hayley
authors.initials: H
authors.lastname: Bridgeman
authors.affiliation: Oral Immunity and Inflammation Unit, NIDCR, NIH, Bethesda, MD 20892, USA.
authors.forename: Teresa
authors.initials: T
authors.lastname: Greenwell-Wild
authors.affiliation: Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PT, UK; Manchester Collaborative Centre for Inflammation Research (MCCIR), University of Manchester, Manchester M13 9NT, UK.
authors.forename: Tamsin
authors.initials: T
authors.lastname: Zangerle-Murray
authors.affiliation: Manchester Collaborative Centre for Inflammation Research (MCCIR), University of Manchester, Manchester M13 9NT, UK.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Fife
authors.affiliation: Immunity at Barrier Sites Initiative, NIAID, NIH, Bethesda, MD 20892, USA; Mucosal Immunology Section, Laboratory of Parasitic Diseases, NIAID, NIH, Bethesda, MD 20892, USA.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Bouladoux
authors.affiliation: Manchester Collaborative Centre for Inflammation Research (MCCIR), University of Manchester, Manchester M13 9NT, UK.
authors.forename: Holly
authors.initials: H
authors.lastname: Linley
authors.affiliation: Oral Immunity and Inflammation Unit, NIDCR, NIH, Bethesda, MD 20892, USA.
authors.forename: Laurie
authors.initials: L
authors.lastname: Brenchley
authors.affiliation: Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PT, UK; Manchester Collaborative Centre for Inflammation Research (MCCIR), University of Manchester, Manchester M13 9NT, UK.
authors.forename: Kelly
authors.initials: K
authors.lastname: Wemyss
authors.affiliation: Oral Immunity and Inflammation Unit, NIDCR, NIH, Bethesda, MD 20892, USA.
authors.forename: Gloria
authors.initials: G
authors.lastname: Calderon
authors.affiliation: Division of Periodontology, Department of Oral Health and Diagnostic Sciences, UConn Health Center, Farmington, CT 06030, USA.
authors.forename: Bo-Young
authors.initials: BY
authors.lastname: Hong
authors.affiliation: Fungal Pathogenesis Unit, NIAID, NIH, Bethesda, MD 20892, USA.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Break
authors.affiliation: Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON L8N 3Z5, Canada.
authors.forename: Dawn M E
authors.initials: DME
authors.lastname: Bowdish
authors.affiliation: Fungal Pathogenesis Unit, NIAID, NIH, Bethesda, MD 20892, USA.
authors.forename: Michail S
authors.initials: MS
authors.lastname: Lionakis
authors.affiliation: Institute of Infection and Immunity, School of Medicine, Cardiff University, Cardiff CF14 4XN, UK.
authors.forename: Simon A
authors.initials: SA
authors.lastname: Jones
authors.affiliation: Cancer and Inflammation Program, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USA.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Trinchieri
authors.affiliation: Division of Periodontology, Department of Oral Health and Diagnostic Sciences, UConn Health Center, Farmington, CT 06030, USA.
authors.forename: Patricia I
authors.initials: PI
authors.lastname: Diaz
authors.affiliation: Immunity at Barrier Sites Initiative, NIAID, NIH, Bethesda, MD 20892, USA; Mucosal Immunology Section, Laboratory of Parasitic Diseases, NIAID, NIH, Bethesda, MD 20892, USA.
authors.forename: Yasmine
authors.initials: Y
authors.lastname: Belkaid
authors.affiliation: Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PT, UK; Manchester Collaborative Centre for Inflammation Research (MCCIR), University of Manchester, Manchester M13 9NT, UK. Electronic address: joanne.konkel@manchester.ac.uk.
authors.forename: Joanne E
authors.initials: JE
authors.lastname: Konkel
authors.affiliation: Oral Immunity and Inflammation Unit, NIDCR, NIH, Bethesda, MD 20892, USA. Electronic address: nmoutsopoulos@dir.nidr.nih.gov.
authors.forename: Niki M
authors.initials: NM
authors.lastname: Moutsopoulos
mesh_terms: D000818:Animals; D005434:Flow Cytometry; D005881:Gingiva / Q000276:immunology* / Q000382:microbiology; D006801:Humans; D018928:Immunity, Mucosal / Q000276:immunology*; D007157:Immunologic Surveillance / Q000276:immunology*; D008409:Mastication; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D064307:Microbiota; D009061:Mouth Mucosa / Q000276:immunology* / Q000382:microbiology; D060888:Real-Time Polymerase Chain Reaction; D058504:Th17 Cells / Q000276:immunology*
keywords: IL-17; T cells; Th17 cells; barrier immunity; mucosal immunology; oral immunity; periodontitis