| First Author | Arizon M | Year | 2012 |
| Journal | Proc Natl Acad Sci U S A | Volume | 109 |
| Issue | 18 | Pages | 7043-8 |
| PubMed ID | 22509018 | Mgi Jnum | J:183918 |
| Mgi Id | MGI:5319561 | Doi | 10.1073/pnas.1116770109 |
| Citation | Arizon M, et al. (2012) Langerhans cells down-regulate inflammation-driven alveolar bone loss. Proc Natl Acad Sci U S A 109(18):7043-8 |
| abstractText | 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-kappaB 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-gamma 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-gamma secretion and excessive activation of RANKL(+)CD4(+) T cells with a capability of promoting osteoclastogenesis. |
