IADR Abstract Archives
Langerhans Cells Orchestrate Initial Establishment of Oral Mucosal Immunity Postnatally
Objectives: We have recently demonstrated the unique neonatal mechanisms induced by the permeable oral epithelium to protect it from bacterial invasion until weaning, a period when the epithelium seals and matures. It is unclear, however, how oral homeostasis is first established after birth. Here, we examined the role of Langerhans cells (LCs), the exclusive antigen-presenting cells of the oral epithelium, in this essential early-life process.
Methods: Langerin-DTR mice were used to deplete LCs in vivo (n=5-10 mice), and flow cytometry and RT-PCR analyses were employed to examine oral immunity. The evaluation of the alveolar bone was performed by micro-computed tomography (µCT) and tartrate-resistant acid phosphatase (TRAP) staining.
Results: Longitudinal postnatal flow cytometry analysis revealed that LCs populate the epithelium mainly during weaning. These newly differentiated LCs efficiently migrated to the lymph node, the site where adaptive immunity is initiated. In fact, higher percentages of LCs were migrated to the lymph node during weaning compared to adulthood. Conditional depletion of LCs at the weaning period resulted in reduced frequencies of FOXP3+ T regulatory cells in the adult gingiva. Further analysis revealed that LC ablation reduced the expression of pro-inflammatory cytokines such as TNF-α and CXCL1, the latter known to mediate neutrophil recruitment. Consequently, the frequencies of neutrophils and monocytes decreased in the gingiva of adult mice due to the depletion of LCs. The quantification of the alveolar bone in adult mice demonstrated a larger bone volume in LC-ablated mice, which was explained by lower numbers of osteoclasts.
Conclusions: Our findings propose a fundamental role of LCs during weaning that control the initial establishment of oral mucosal homeostasis in adulthood. This LC-mediated gingival immunity can nevertheless cause bone loss, exemplifying the nature of this delicate immunological balance characterized as spontaneous bone loss.
Methods: Langerin-DTR mice were used to deplete LCs in vivo (n=5-10 mice), and flow cytometry and RT-PCR analyses were employed to examine oral immunity. The evaluation of the alveolar bone was performed by micro-computed tomography (µCT) and tartrate-resistant acid phosphatase (TRAP) staining.
Results: Longitudinal postnatal flow cytometry analysis revealed that LCs populate the epithelium mainly during weaning. These newly differentiated LCs efficiently migrated to the lymph node, the site where adaptive immunity is initiated. In fact, higher percentages of LCs were migrated to the lymph node during weaning compared to adulthood. Conditional depletion of LCs at the weaning period resulted in reduced frequencies of FOXP3+ T regulatory cells in the adult gingiva. Further analysis revealed that LC ablation reduced the expression of pro-inflammatory cytokines such as TNF-α and CXCL1, the latter known to mediate neutrophil recruitment. Consequently, the frequencies of neutrophils and monocytes decreased in the gingiva of adult mice due to the depletion of LCs. The quantification of the alveolar bone in adult mice demonstrated a larger bone volume in LC-ablated mice, which was explained by lower numbers of osteoclasts.
Conclusions: Our findings propose a fundamental role of LCs during weaning that control the initial establishment of oral mucosal homeostasis in adulthood. This LC-mediated gingival immunity can nevertheless cause bone loss, exemplifying the nature of this delicate immunological balance characterized as spontaneous bone loss.