Langerhans cells down-regulate inflammation-driven alveolar bone loss

Moran Arizon, Itay Nudel, Hadas Segev, Gabriel Mizraji, Mazal Elnekave, Karina Furmanov, Luba Eli-Berchoer, Björn E. Clausen, Lior Shapira, Asaf Wilensky, Avi Hai Hovav*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

60 Scopus citations

Abstract

Excessive bone resorption is frequently associated with chronic infections and inflammatory diseases. Whereas T cells were demonstrated to facilitate osteoclastogenesis in such diseases, the role of dendritic cells, the most potent activators of naive T cells, remains unclear. Using a model involving inflammation-driven alveolar bone loss attributable to infection, we showed that in vivo ablation of Langerhans cells (LCs) resulted in enhanced bone loss. An increased infiltration of B and T lymphocytes into the tissue surrounding the bone was observed in LC-ablated mice, including receptor activator of NF-κB ligand (RANKL)-expressing CD4+ T cells with known capabilities of altering bone homeostasis. In addition, the absence of LCs significantly reduced the numbers of CD4+Foxp3+ T-regulatory cells in the tissue. Further investigation revealed that LCs were not directly involved in presenting antigens to T cells. Nevertheless, despite their low numbers in the tissue, the absence of LCs resulted in an elevated activation of CD4+ but not CD8+ T cells. This activation involved elevated production of IFN-γ but not IL-17 or IL-10 cytokines. Our data, thus, reveal a protective immunoregulatory role for LCs in inflammation-induced alveolar bone resorption, by inhibiting IFN-γ secretion and excessive activation of RANKL+CD4+ T cells with a capability of promoting osteoclastogenesis.

Original languageAmerican English
Pages (from-to)7043-7048
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue number18
DOIs
StatePublished - 1 May 2012

Keywords

  • Experimental periodontitis
  • Oral mucosa
  • Osteoimmunology
  • Porphyromonas gingivalis

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