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For personal use only. ANRV270-IY24-02 12:28 Figure 3 Schematic summary of bone cell differentiation. Mesenchymal stem cells, which also give rise to myoblasts, adipocytes, chondrocytes, and some as yet uncharacterized stromal cells (also called marrow stromal cells, marrow fibroblasts, or the reticular network), differentiate into preosteoblasts and then become OBs on the bone surface. OBs either incorporate into bone as osteocytes or remain on the surface as lining cells. A common myeloid lineage precursor, which can also give rise to macrophages and dendritic cells, commits to becoming a preosteoclast and then fuses to become a mature, multinucleated osteoclast.

Kopcow HD, Allan DS, Ge B, Rybalov B, Andzelm MM, et al. 2005. Human decidual NK cells form immature activating synapses and are not cytotoxic. Proc. Natl. Acad. Sci. USA. 43:15563–68 94. Skare J, Strominger JL. 1980. Cloning and mapping of BamHi endonuclease fragments of DNA from the transforming B95-8 strain of Epstein-Barr virus. Proc. Natl. Acad. Sci. USA 77:3860–64 95. Schaefer BC, Woisetschlaeger M, Strominger JL, Speck SH. 1991. Exclusive expression of Epstein-Barr virus nuclear antigen 1 in Burkitt lymphoma arises from a third promoter, distinct from the promoters used in latently infected lymphocytes.

TRANCE may also be involved in actively inducing tolerance. TRANCE signaling has been directly implicated in the induction of oral tolerance in mice. Feeding low-dose ovalbumin to mice concomitant with intravenous TRANCE treatment results in T cells refractory to rechallenge and correlates with in vitro production of the suppressive cytokine IL-10 by mucosal DCs (103). Another study has demonstrated that TRANCEmediated signaling is required to prevent the onset of autoimmune disease in a TNF-αinducible mouse model of diabetes and that blockade of TRANCE-RANK interactions parallel a diminution of CD4+ CD25+ regulatory lymphocytes, which are necessary to prevent CTL-mediated islet cell destruction (104).

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