Langerhans cells down-regulate inflammation-driven alveolar bone loss

被引:64
作者
Arizon, Moran [1 ]
Nudel, Itay [1 ]
Segev, Hadas [1 ]
Mizraji, Gabriel [1 ]
Elnekave, Mazal [1 ]
Furmanov, Karina [1 ]
Eli-Berchoer, Luba [1 ]
Clausen, Bjorn E. [3 ]
Shapira, Lior [2 ]
Wilensky, Asaf [2 ]
Hovav, Avi-Hai [1 ]
机构
[1] Hebrew Univ Jerusalem, Hadassah Sch Dent Med, Inst Dent Sci, IL-91120 Jerusalem, Israel
[2] Hebrew Univ Jerusalem, Hadassah Sch Dent Med, Dept Periodontol, IL-91120 Jerusalem, Israel
[3] Univ Med Ctr, Erasmus Med Ctr, Dept Immunol, NL-3015 GE Rotterdam, Netherlands
基金
以色列科学基金会;
关键词
osteoimmunology; Porphyromonas gingivalis; oral mucosa; experimental periodontitis; CD4(+) T-CELLS; DERMAL DENDRITIC CELLS; EXPERIMENTAL PERIODONTITIS; RECEPTOR ACTIVATOR; GAMMA-INTERFERON; OSTEOPROTEGERIN LIGAND; ORAL-MUCOSA; IFN-GAMMA; IN-VIVO; MICE;
D O I
10.1073/pnas.1116770109
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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-kappa B 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.
引用
收藏
页码:7043 / 7048
页数:6
相关论文
共 50 条
[1]   Molecular pathways regulating CD4+ T cell differentiation, anergy and memory with implications for vaccines [J].
Ahlers, Jeffrey D. ;
Belyakov, Igor M. .
TRENDS IN MOLECULAR MEDICINE, 2010, 16 (10) :478-491
[2]   Distribution of Langerhans cells and mast cells within the human oral mucosa: new application sites of allergens in sublingual immunotherapy? [J].
Allam, J. -P. ;
Stojanovski, G. ;
Friedrichs, N. ;
Peng, W. ;
Bieber, T. ;
Wenzel, J. ;
Novak, N. .
ALLERGY, 2008, 63 (06) :720-727
[3]   Migratory dendritic cells transfer antigen to a lymph node-resident dendritic cell population for efficient CTL priming [J].
Allan, Rhys S. ;
Waithman, Jason ;
Bedoui, Sammy ;
Jones, Claerwen M. ;
Villadangos, Jose A. ;
Zhan, Yifan ;
Lew, Andrew M. ;
Shortman, Ken ;
Heath, William R. ;
Carbone, Francis R. .
IMMUNITY, 2006, 25 (01) :153-162
[4]   Immune interactions with CD4+ T cells promote the development of functional osteoclasts from murine CD11c+ dendritic cells [J].
Alnaeeli, Mawadda ;
Penninger, Josef M. ;
Teng, Yen-Tung Andy .
JOURNAL OF IMMUNOLOGY, 2006, 177 (05) :3314-3326
[5]   CD4+ T cells and the proinflammatory cytokines gamma interferon and interleukin-6 contribute to alveolar bone loss in mice [J].
Baker, PJ ;
Dixon, M ;
Evans, RT ;
Dufour, L ;
Johnson, E ;
Roopenian, DC .
INFECTION AND IMMUNITY, 1999, 67 (06) :2804-2809
[6]   Epidermal receptor activator of NF-κB ligand controls Langerhans cells numbers and proliferation [J].
Barbaroux, Jean-Baptiste O. ;
Beleut, Manfred ;
Brisken, Cathrin ;
Mueller, Christopher G. ;
Groves, Richard W. .
JOURNAL OF IMMUNOLOGY, 2008, 181 (02) :1103-1108
[7]   Cross-presentation of viral and self antigens by skin-derived CD103+ dendritic cells [J].
Bedoui, Sammy ;
Whitney, Paul G. ;
Waithman, Jason ;
Eidsmo, Liv ;
Wakim, Linda ;
Caminschi, Irina ;
Allan, Rhys S. ;
Wojtasiak, Magdalena ;
Shortman, Ken ;
Carbone, Francis R. ;
Brooks, Andrew G. ;
Heath, William R. .
NATURE IMMUNOLOGY, 2009, 10 (05) :488-495
[8]   Inducible ablation of mouse Langerhans cells diminishes but fails to abrogate contact hypersensitivity [J].
Bennett, CL ;
van Rijn, E ;
Jung, S ;
Inaba, K ;
Steinman, RM ;
Kapsenberg, ML ;
Clausen, BE .
JOURNAL OF CELL BIOLOGY, 2005, 169 (04) :569-576
[9]   Osteoimmunology - The hidden immune regulation of bone [J].
Caetano-Lopes, J. ;
Canhao, H. ;
Fonseca, J. E. .
AUTOIMMUNITY REVIEWS, 2009, 8 (03) :250-255
[10]   Variable carbohydrate modifications to the catalytic chains of the RgpA and RgpB proteases of Porphyromonas gingivalis W50 [J].
Curtis, MA ;
Thickett, A ;
Slaney, JM ;
Rangarajan, M ;
Aduse-Opoku, J ;
Shepherd, P ;
Paramonov, N ;
Hounsell, EF .
INFECTION AND IMMUNITY, 1999, 67 (08) :3816-3823