Growth Factor-Induced Mobilization of Dendritic Cells in Kidney and Liver of Rhesus Macaques: Implications for Transplantation

Morelli, Adrián E.; Coates, P. Toby; Shufesky, William J.; Barratt‐Boyes, Simon M.; Fung, John J.; Demetris, Anthony J.; Thomson, Angus W.

doi:10.1097/01.tp.0000255320.00061.e9

Cited by 18 publications

(14 citation statements)

References 27 publications

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“…Future studies will be needed to address these issues as well as to determine if findings in mice apply to humans, given the immunologic differences anticipated in scale up from mice to men, as recognized in hemophilia gene transfer [29]. The recent successful induction of transplant tolerance by immature DC in mouse transplant models, is currently being studied in larger animal models [30], including rhesus monkeys; and a clinical trial of immature DC, shown to be successful in the treatment of diabetes in mouse models has been initiated in patients with type 1 diabetes [31]. Hopefully, these preliminary studies of DC immunotherapy will provide preliminary insights into the application of this strategy in the prevention and suppression of anti-F.VIII antibodies in individuals with hemophilia.…”

Section: Discussionmentioning

confidence: 99%

Factor VIII−pulsed dendritic cells reduce anti−factor VIII antibody formation in the hemophilia A mouse model

Ragni¹,

Wu²,

Liang³

et al. 2009

Experimental Hematology

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Objective Hemophilia inhibitor formation is a T-cell dependent immune response to infused factor VIII (F.VIII). As immature dendritic cells (DCre) regulate immune response and promote tolerance, we evaluated F.VIII-pulsed DCre, propagated from bone marrow in the presence of GM-CSF and TGFβ, in achieving F.VIII tolerance. Methods The effects of intravenous F.VIII-pulsed DCre in C57BL/6 hemophilia A mice were determined by total F.VIII inhibitory antibodies, T cell proliferation, thymidine uptake, cytokine profile, and surface molecule expression. Results After tail vein injection of 2.5 U recombinant F.VIII (rF.VIII) on day 0, 2, and 4, anti-F.VIII antibody peaked on day 6, and increased further on day 17 following rF.VIII re-challenge on day 12, 14, and 16, with increased T cell proliferative response to in vitro F.VIII. When mice were pretreated with 2×106 F.VIII-pulsed immature DCre (deficient NF-kB nuclear protein binding, low CD80, low CD86, high IL-10 phenotype) 7 days before rF.VIII challenge, anti-F.VIII was reduced on day 6 and on day 8, 0.1±0.0 BU/ml (Bethesda units/ml) vs. control PBS-treated hemophilia A mice, 2.0±0.1 BU/ml, p<0.01. Re-challenge with rF.VIII on day 12 produced no increase in anti-F.VIII antibody response. This was associated with high serum IL-10 and low IL-2 levels by ELISA, and splenic T cell hyporesponsivess to F.VIII, with IL-10 production, high FoxP3 expression by qT-PCR, and T regulatory cell expansion, confirmed in OVA-TCR transgenic mice. Conclusions These findings suggest F.VIII-pulsed DCre reduce anti-F.VIII antibody formation in hemophilia A mice by induction of regulatory T cell-mediated hyporesponsiveness of T helper cells to F.VIII.

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Section: Discussionmentioning

confidence: 99%

Factor VIII−pulsed dendritic cells reduce anti−factor VIII antibody formation in the hemophilia A mouse model

Ragni¹,

Wu²,

Liang³

et al. 2009

Experimental Hematology

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“…45 In human renal allografts and in IgA nephropathy, a very low number of DC-SIGN-positive cells were described in the glomeruli (1/50 and 1/12, respectively). 15 In contrast, Morelli et al 46 described an accumulation of DCs in the glomeruli and the tubulointerstitium in non-human primates after mobilization with Fmslike tyrosine kinase 3 ligand. Our results are applicable to only those antigens used here, particularly DC-SIGN, and we cannot rule out a DC-SIGN-negative population of intraglomerular DCs.…”

Section: Dc-sign Facilitates Interaction With Resting T Cells (Via Icmentioning

confidence: 95%

Compartment specific expression of dendritic cell markers in human glomerulonephritis

Segerer¹,

Heller²,

Lindenmeyer³

et al. 2008

Kidney International

119

133

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Macrophages and dendritic cells are heterogenous and highly plastic bone marrow-derived cells that play major roles in renal diseases. We characterized these cells using immunohistochemistry in 55 renal biopsies from control patients or patients with glomerulonephritis as an initial step towards postulating specific roles for these cells in kidney disease. In proliferative glomerulonephritis numerous CD68 positive (pan monocyte, macrophage and dendritic marker) cells were found in both glomeruli and the tubulointerstitial space, however, a myeloid dendritic cell marker (DC-SIGN) was identified only in the tubulointerstitium. A significant number of plasmacytoid dendritic cells (identified as BDCA-2 positive cells) were seen at sites of interstitial inflammation, including follicular aggregates of inflammatory cells. Langerin positive cells (a marker of Langerhans' cells) were detectable but rare. The area of either CD68 or DC-SIGN positive interstitial cells correlated with serum creatinine. Low levels of DC-SIGN, DC-LAMP and MHC class II mRNA were present in the tubulointerstitial space in controls and increased only in that region in proliferative glomerulonephritis. We demonstrate that the CD68 positive cells infiltrating the glomerulus lack dendritic cell markers (reflecting macrophages), whereas in the tubulointerstitial space the majority of CD68 positive cells are also DC-SIGN positive (reflecting myeloid dendritic cells). Their number correlated with serum creatinine, which further emphasizes the significance of interstitial DCs in progressive glomerular diseases.

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“…Systemic administration of Flt3L to mice55 and non-human primates56 has enabled expansion of both renal cDC and pDC in vivo . Ex vivo, freshly-isolated mobilized DC retain an immature phenotype and promote CD4 + CD25 + IL-10-producing regulatory T cells (Treg) 55.…”

Section: Renal DC and Mac In Homeostasismentioning

confidence: 99%

Dendritic cells and macrophages in the kidney: a spectrum of good and evil

et al. 2014

Self Cite

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Renal dendritic cells (DC) and macrophages (Mac) represent a constitutive, extensive and contiguous network of innate immune cells that provide sentinel and immune intelligence function. They induce and regulate inflammatory responses to freely-filtered antigenic material and protect the kidney from infection. Tissue–resident or infiltrating DC and Mac are key to the initiation and propagation of renal disease, as well as essential contributors to subsequent tissue regeneration regardless of its etiology and pathogenesis. Their identification, functional and phenotypic distinction, interplay and relationship with effector and regulatory adaptive immune cells is complex and incompletely understood. This review discusses both the common and distinct characteristics of these cells, as well as recent key advances in the field that have identified renal-specific functions of DC and Mac that enable these important, phagocytic, antigen-presenting, cells to mediate or mitigate intrinsic kidney disease. We also identify priority areas for further investigation and prospects for translational and therapeutic application of acquired knowledge.

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Growth Factor-Induced Mobilization of Dendritic Cells in Kidney and Liver of Rhesus Macaques: Implications for Transplantation

Cited by 18 publications

References 27 publications

Factor VIII−pulsed dendritic cells reduce anti−factor VIII antibody formation in the hemophilia A mouse model

Factor VIII−pulsed dendritic cells reduce anti−factor VIII antibody formation in the hemophilia A mouse model

Compartment specific expression of dendritic cell markers in human glomerulonephritis

Dendritic cells and macrophages in the kidney: a spectrum of good and evil

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