Osteopetroses and immunodeficiencies in humans.
OBJECTIVE
This review focuses on human and murine pathologies involving both osteoclasts and immune cells. These diseases have been relevant to the discovery of novel interactions and pathways shared between these two types of cells.


RESULTS
Interactions between immune cells and osteoclasts were originally shown in murine models by gene targeting of molecules involved in the early steps of osteoclast differentiation, since receptor activator of nuclear factor kappa-B ligand (RANKL), RANK and TNFR-associated factor 6 knockout mice bore abnormalities of both bone resorption and immune system. Subsequently, osteoclast stimulation by RANKL secreted by lymphocytes in autoimmune diseases, such as rheumatoid arthritis, was found. More recently, the identification of immunoreceptor tyrosine-based activation motif receptors and adaptors important for both dendritic cells and osteoclast function has established a link between innate and adaptive immunity and bone. Finally, osteoclasts are also important for hematopoietic stem-cell mobilization, providing a further level of regulation of lymphoid cells.


CONCLUSIONS
These findings open up a new field of research, osteoimmunology, which will unravel previously unsuspected links between bone remodelling and the immune response.
Villa
Anna
A
Istituto Tecnologie Biomediche, CNR, Segrate, Italy. anna.villa@itb.cnr.it
Vezzoni
Paolo
P
Frattini
Annalisa
A
D000818:Animals; D001862:Bone Resorption / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics* / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology / Q000473:pathology; D006412:Hematopoietic Stem Cells / Q000276:immunology / Q000473:pathology; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics*; D007153:Immunologic Deficiency Syndromes / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D008214:Lymphocytes / Q000276:immunology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D010010:Osteoclasts / Q000276:immunology / Q000473:pathology; D010022:Osteopetrosis / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D053245:RANK Ligand / Q000235:genetics / Q000276:immunology; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000235:genetics / Q000276:immunology
D015815:Cell Adhesion Molecules; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C072273:TNFAIP6 protein, human; C505686:TNFRSF11A protein, human; C505688:TNFSF11 protein, human