On-going Mechanical Damage from Mastication Drives Homeostatic Th17 Cell Responses at the Oral Barrier

Immunity. 2017 Jan 17;46(1):133-147. doi: 10.1016/j.immuni.2016.12.010. Epub 2017 Jan 10.

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.

Keywords: IL-17; T cells; Th17 cells; barrier immunity; mucosal immunology; oral immunity; periodontitis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Flow Cytometry
  • Gingiva / immunology*
  • Gingiva / microbiology
  • Humans
  • Immunity, Mucosal / immunology*
  • Immunologic Surveillance / immunology*
  • Mastication
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microbiota
  • Mouth Mucosa / immunology*
  • Mouth Mucosa / microbiology
  • Real-Time Polymerase Chain Reaction
  • Th17 Cells / immunology*