Current Print IssueJournal of Experimental Medicine RSS feed -- current issueFollicular dendritic cells control engulfment of apoptotic bodies by secreting Mfge8- June 9, 2008 The secreted phosphatidylserine-binding protein milk fat globule epidermal growth factor 8 (Mfge8) mediates engulfment of apoptotic germinal center B cells by tingible-body macrophages (TBMs). Impairment of this process can contribute to autoimmunity. We show that Mfge8 is identical to the mouse follicular dendritic cell (FDC) marker FDC-M1. In bone-marrow chimeras between wild-type and Mfge8–– mice, all splenic Mfge8 was derived from FDCs rather than TBMs. However,...http://www.jem.org/cgi/content/short/205/6/1293?rss=1 Membrane traffic and turnover in TRP-ML1-deficient cells: a revised model for mucolipidosis type IV pathogenesis- June 9, 2008 The lysosomal storage disorder mucolipidosis type IV (MLIV) is caused by mutations in the transient receptor potential–mucolipin-1 (TRP-ML1) ion channel. The "biogenesis" model for MLIV pathogenesis suggests that TRP-ML1 modulates postendocytic delivery to lysosomes by regulating interactions between late endosomes and lysosomes. This model is based on observed lipid trafficking delays in MLIV patient fibroblasts. Because membrane traffic aberrations may be secondary to lipid buildup in...http://www.jem.org/cgi/content/short/205/6/1477?rss=1 Divergent roles of endothelial NF-kappaB in multiple organ injury and bacterial clearance in mouse models of sepsis- June 9, 2008 To define the roles of endothelial-intrinsic nuclear factor B (NF-B) activity in host defense and multiple organ injury in response to sepsis, we generated double transgenic (TG) mice (EC-rtTAI-Bmt) that conditionally overexpress a degradation-resistant form of the NF-B inhibitor I-B (I-Bmt) selectively on vascular endothelium. The EC-rtTAI-Bmt mice had no basal, but a relatively high level of doxycycline-inducible, I-Bmt expression. I-Bmt expression was detected in endothelial cells, but not...http://www.jem.org/cgi/content/short/205/6/1303?rss=1 OX40 triggering blocks suppression by regulatory T cells and facilitates tumor rejection- June 9, 2008http://www.jem.org/cgi/content/short/205/6/1505?rss=1 Constitutive CD40 signaling in B cells selectively activates the noncanonical NF-kappaB pathway and promotes lymphomagenesis- June 9, 2008 CD40, a member of the tumor necrosis factor (TNF) receptor family, plays an essential role in T cell–dependent immune responses. Because CD40 is widely expressed on the surface of tumor cells in various B cell malignancies, deregulated CD40 signaling has been suggested to contribute to lymphomagenesis. In this study, we show that B cell-specific expression of a constitutively active CD40 receptor, in the form of a latent membrane protein 1 (LMP1)CD40 chimeric protein, promoted an increase.http://www.jem.org/cgi/content/short/205/6/1317?rss=1 IKKbetaNF-kappaB and the miscreant macrophage- June 9, 2008 Macrophage activation relies on complex intracellular signaling processes that integrate the need for rapid inflammatory responses to pathogens with the need to resolve inflammation without permanent harm to normal tissues. Patterns of aberrant macrophage activation characterize and sustain disorders of chronic inflammation, infection, and cancer. New studies now show a role for the NF-B activator IKKβ in promoting an alternative, immunosuppressive pattern of macrophage activation, which...http://www.jem.org/cgi/content/short/205/6/1255?rss=1 P2X7 receptors on osteoblasts couple to production of lysophosphatidic acid: a signaling axis promoting osteogenesis- June 9, 2008http://www.jem.org/cgi/content/short/205/6/i15?rss=1 Sheepish B cells: evidence for antigen-independent antibody diversification in humans and mice- June 9, 2008 Antibody diversity is first generated by rearrangement of immunoglobulin (Ig) genes during B cell development in the bone marrow, and later by antigen-driven diversification in germinal centers (GCs). New data in humans and mice now identify specific B cell populations that may have undergone antigen-independent hypermutation outside GCs.http://www.jem.org/cgi/content/short/205/6/1251?rss=1 The VEGF receptor Flt-1 spatially modulates Flk-1 signaling and blood vessel branching- June 9, 2008http://www.jem.org/cgi/content/short/205/6/i16?rss=1 Breaking tolerance to the natural human liver autoantigen cytochrome P450 2D6 by virus infection- June 9, 2008 Autoimmune liver diseases, such as autoimmune hepatitis (AIH) and primary biliary cirrhosis, often have severe consequences for the patient. Because of a lack of appropriate animal models, not much is known about their potential viral etiology. Infection by liver-tropic viruses is one possibility for the breakdown of self-tolerance. Therefore, we infected mice with adenovirus Ad5 expressing human cytochrome P450 2D6 (Ad-2D6). Ad-2D6–infected mice developed persistent autoimmune liver...http://www.jem.org/cgi/content/short/205/6/1409?rss=1 |