title: Langerhans cells down-regulate inflammation-driven alveolar bone loss.
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.
authors.affiliation: Institute of Dental Sciences, Hebrew University-Hadassah School of Dental Medicine, Jerusalem 91120, Israel.
authors.forename: Moran
authors.initials: M
authors.lastname: Arizon
authors.forename: Itay
authors.initials: I
authors.lastname: Nudel
authors.forename: Hadas
authors.initials: H
authors.lastname: Segev
authors.forename: Gabriel
authors.initials: G
authors.lastname: Mizraji
authors.forename: Mazal
authors.initials: M
authors.lastname: Elnekave
authors.forename: Karina
authors.initials: K
authors.lastname: Furmanov
authors.forename: Luba
authors.initials: L
authors.lastname: Eli-Berchoer
authors.forename: Björn E
authors.initials: BE
authors.lastname: Clausen
authors.forename: Lior
authors.initials: L
authors.lastname: Shapira
authors.forename: Asaf
authors.initials: A
authors.lastname: Wilensky
authors.forename: Avi-Hai
authors.initials: AH
authors.lastname: Hovav
mesh_terms: D016301:Alveolar Bone Loss / Q000209:etiology / Q000276:immunology* / Q000517:prevention & control*; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D016866:Bacteroidaceae Infections / Q000150:complications / Q000276:immunology; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D017931:DNA Primers / Q000235:genetics; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000276:immunology; D066257:Heparin-binding EGF-like Growth Factor; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000276:immunology; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D007801:Langerhans Cells / Q000145:classification / Q000276:immunology*; D037181:Lectins, C-Type / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation; D037241:Mannose-Binding Lectins / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016966:Porphyromonas gingivalis / Q000276:immunology; D053245:RANK Ligand / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
chemical_list: D015703:Antigens, CD; C121916:CD207 protein, human; D017931:DNA Primers; C587883:HBEGF protein, human; C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; C556062:IL10 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D020381:Interleukin-17; D037181:Lectins, C-Type; D037241:Mannose-Binding Lectins; D053245:RANK Ligand; C505689:Tnfsf11 protein, mouse; D016753:Interleukin-10; D007371:Interferon-gamma