G J Randolph

..Indeed, MRP1 and the related multidrug resistance protein 1 (MDR1, p-glycoprotein, ABCB1) may control the intracellular and extracellular accumulation of key signaling lipids that regulate dendritic cell migration...

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..All of these points of intervention will be briefly discussed in this article...

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..We propose that CD16(+) monocytes may contribute significantly to precursors for DCs that transiently survey tissues and migrate to lymph nodes via afferent lymphatic vessels...

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..Finally, to gain a more molecular appreciation of the specialized migratory properties of DCs, we review the signaling cascades that govern the process of DC migration...

..This review compares the fate of monocyte-derived cells that enter atherosclerotic plaques with those that accumulate at other sites of inflammation...

..Monocytes that remained in the subendothelial matrix became macrophages. Therefore, monocytes have two potential fates associated with distinct patterns of migration...

..Thus, MRP-1 regulates DC migration to lymph nodes, apparently by transporting LTC(4), which in turn promotes chemotaxis to CCL19 and mobilization of DCs from the epidermis...

..Overall, these data demonstrate that the two circulating subsets of monocytes give rise to distinct tissue DC populations...

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..These data reveal that immature monocytes unexpectedly sample antigen from the bone marrow environment and that they can present these antigens after they leave the bone marrow...

..Instead, our analysis suggests that nonlymphoid organ DCs comprise a major population of DCs within lymph nodes only after introduction of an inflammatory stimulus...

..Further cDC development involves cell division, which is controlled in part by regulatory T cells and fms-like tyrosine kinase receptor-3...

..When these monocyte-derived DCs exit skin to emigrate to LNs, they use not only CCR7 but also CCR8, which was not previously recognized to participate in migration to LNs...

..Altogether, these results underline the diverse origin of the lamina propria DC network and identify mucosal DCs that arise from pre-DCs as key sentinels of the gut immune system...

..These data reveal a way in which migratory monocyte-derived DCs and other DCs, like lymph node resident DCs, both mediate cross-presentation...

..We postulate that a major source of DC in lymph nodes is cells derived from monocytes that enter a tissue via the blood and leave several days later via afferent lymphatic channels...

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..Thus, a substantial minority of inflammatory monocytes carry phagocytosed particles to lymph nodes and differentiate into DCs...

..This binding was blocked by anti-TF MoAb, suggesting that endothelial cells bear a receptor for TF. These data suggest that mononuclear phagocytes use TF, perhaps as an adhesive protein, to exit sites of inflammation...

..This finding suggests that changes in the physical presentation of the same antigen delivered to the airway during natural immune responses or vaccinations may markedly affect the character of the T cell response that ensues...

..We propose that alterations in the numbers or function of monocytes and DC coupled to dysregulated expression of chemokines in the neural tissues, favors development of CNS autoimmune disease...

..Fortunately, the rate of progress in the study of monocyte fate is rapidly picking up pace, giving rise to the expectation that we will soon know much more about the biology of monocytes in the steady state and inflammation...

..However, when infected with live influenza virus, the role of type I IFN in mediating differentiation and Ag-presenting capacity is expendable, apparently due to other mechanisms of virus-mediated activation...

..In this context, HDL and PAFAH maintain a normally functional DC compartment...

..These results identify Gr-1(hi) monocytes as the direct precursors for LCs in vivo and establish the importance of the CSF-1 receptor in this process...

..Thus, alloantigen-presenting pDCs home to the lymph nodes in tolerogenic conditions, where they mediate alloantigen-specific Treg cell development and allograft tolerance...

..Knowledge that DC migration from the periphery is augmented by B cell-dependent signals reveals new potential strategies to increase DC migration during vaccination...

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..Taken with the other gene expression data, these results in vivo point to complex relationships among the immune system, nuclear hormone receptors, and inflammation during regression...

..The findings indicate that ABCA1, ABCG1, and HDL inhibit the proliferation of hematopoietic stem and multipotential progenitor cells and connect expansion of these populations with leukocytosis and accelerated atherosclerosis...

..Finally, we discuss how this knowledge may be useful clinically, emphasizing that CX3CR1 may in particular be a viable target for therapeutic manipulation of monocyte-derived cell fate in cardiovascular disease...

..Our protocol describes how to label and track pulmonary dendritic cells from the airway and lung to the mediastinal lymph nodes and reveals how to avoid pitfalls and suboptimal assays...

..This study demonstrates the ability to reroute HDL from its natural targets to tumor blood vessels and its potential for multimodal imaging of tumor-associated processes...

..Together, these data demonstrate a direct role of LECs in the modulation of immune response and suggest a function of the lymphatic endothelium in preventing undesired immune reactions in inflammatory conditions...

..These results indicate that FTY720- and sphingosine 1-phosphate receptor-stimulated T cell migration are dependent on the restricted usage of chemokine receptor-ligand pairs within discrete anatomic compartments...

..In this issue, Allan et al. (2006) conclude that transport of herpes-virus antigens to lymph nodes by dendritic cells is crucial for antiviral immunity, but migrating DCs do not present herpes antigens to CD8(+) lymphocytes...

..Thus, whereas human and mouse monocyte subsets are far more broadly conserved than currently recognized, important differences between the species deserve consideration when models of human disease are studied in mice...

..Thus, antagonizing CX3CR1 may be effective therapeutically in ameliorating CCR2(+) monocyte recruitment to plaques without impairing their CCR2-dependent responses to inflammation overall...

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..While strictly controlled in the blood by erythrocytes, the high IL-12- and TNF-alpha-producing capacity of slanDC in tissues may be critical in fighting off pathogens; if uncontrolled, it may lead to adverse inflammatory reactions...

..Computational modeling revealed that transcellular gradients of CCR7 ligand were created under flow to drive this response. This illustrates how tumor cells may be guided to lymphatics during metastasis...

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..During attachment, Swap70-/- B cells showed defective polarization and did not form uropods or stabilize lamellipodia at a defined region. Thus, SWAP-70 selectively regulates processes essential for B cell entry into lymph nodes...

..Using nanoparticles conjugated to the model antigen ovalbumin, we demonstrate generation of humoral and cellular immunity in mice in a size- and complement-dependent manner...

..The role of TAF-dependent ECM remodeling and TAF-derived peptide growth factors, cytokines, and chemokines in the immune modulation is stressed and the idea of TAF as an important therapeutic target is emphasized...

..Several promising tools that may ultimately lead to valuable insight into how lymphatic disorders could be treated will be explored in this proposal. ..

..More work is needed to unravel this surprising finding and understand its impact on the immune system (aim 3). ..

..More work is needed to unravel this surprising finding and understand its impact on the immune system (aim 3). ..

..We will study this possibility and its relevance to artery wall DCs that accumulate in prelesional areas. ..

..We will study this possibility and its relevance to artery wall DCs that accumulate in prelesional areas. ..

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..We will study this possibility and its relevance to artery wall DCs that accumulate in prelesional areas. ..

..The second aim will determine whether all monocytes, or just a subset of cells, have the capacity to differentiate into DC. The third aim will explore the roles of the transmembrane transporter proteins in DC migration and maturation. ..

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