Immune cell populations at barrier surfaces such as the skin and gut are regulated by local cues that ensure microbial defence and homeostasis. Yet little is known about the cues regulating immune cells at a key barrier surface in the mouth — the gingiva. A new study shows that mechanical damage from chewing (mastication) promotes an accumulation of T helper 17 (TH17) cells with age. These cells seem to support host protection but when amplified can also contribute to periodontal bone loss.
In healthy individuals, TH17 cells are enriched in gut and skin barrier tissues and are influenced by colonization with commensal microbes. By contrast, few TH17 cells were seen in the gingiva of young (8-week-old) mice. However, by 24 weeks of age (equivalent to middle age), TH17 cell frequencies and total numbers were significantly increased. This age-dependent expansion of gingival TH17 cell populations was independent of oral microbes, because the increase also occurred in germ-free mice and in mice lacking segmented filamentous bacteria (known inducers of TH17 cells in the gut). Also unlike gut or skin TH17 cell development, the authors found no role for interleukin-1 (IL-1) or IL-23 in the development of gingival TH17 cells. Instead, IL-6 was required for gingival TH17 cell accumulation, as mice with T cells lacking IL-6 receptor did not generate TH17 cells in the gingiva.
The authors then investigated whether mechanical damage resulting from mastication could be involved in gingival TH17 cell generation by feeding weanling mice a nutritionally matched soft diet. At 24 weeks of age, mice fed a soft diet showed a significant reduction specifically of gingival TH17 cells compared with mice fed normal chow. Conversely, mice subjected to increased mechanical damage of the gingiva, through rubbing with a cotton applicator every other day or by placing them on a hardened diet, had more gingival TH17 cells than age-matched control mice. The damage-induced increase in TH17 cells was associated with rapid production of IL-6 by epithelial cells in the gingiva.
Finally, the authors showed that physiological damage to the gingiva through mastication and the accumulation of TH17 cells was sufficient to drive the expression of epithelial defensins and neutrophil chemoattractants implicated in host defence. However, a pathogenic consequence for elevated TH17 cells was suggested by the increase in periodontal bone loss observed in 24- compared with 8-week-old wild-type mice but not in 24-week-old IL-17-deficient mice. Together, these data identify physiological and pathological roles for mastication-induced gingival TH17 cells.
ORIGINAL ARTICLE Dutzan, N. et al. On-going mechanical damage from mastication drives homeostatic Th17 cell responses at the oral barrier. Immunity http://dx.doi.org/ 10.1016/j.immuni.2016.12.010 (2017)