%0 Journal Article
%~ PubMed
%A Tian, Xinrui
%A Zhang, Jianlin
%A Tan, Thian Kui
%A Lyons, J Guy
%A Zhao, Hong
%A Niu, Bo
%A Lee, So Ra
%A Tsatralis, Tania
%A Zhao, Ye
%A Wang, Ya
%A Cao, Qi
%A Wang, Changqi
%A Wang, Yiping
%A Lee, Vincent W S
%A Kahn, Michael
%A Zheng, Guoping
%A Harris, David C H
%T Association of β-catenin with P-Smad3 but not LEF-1 dissociates in vitro profibrotic from anti-inflammatory effects of TGF-β1.
%B Journal of Cell Science
%D 2013
%C United Kingdom
%I The Company of Biologists Ltd.
%V 126
%N Pt 1
%P 67-76
%@ 1477-9137
%X 
%Z FOR Codes: 601


%0 Journal Article
%A Lee, Vincent
%A Wang, Yiping
%A Harris, David
%T The role of the immune system in the pathogenesis of hypertension
%B Current Hypertension Reviews
%D 2013
%C Netherlands
%I Bentham Science Publishers Ltd.
%V 9
%N 1
%P 76-84
%@ 1573-4021
%X 
%Z FOR Codes: 110201 110799


%0 Journal Article
%~ PubMed
%A Zhou, Jimmy Jianheng
%A Wang, Yuan Min
%A Lee, Vincent Ws
%A Phoon, Richard Ks
%A Zhang, Geoff Yu
%A Wang, Ya
%A Tan, Thian Kui
%A Hu, Min
%A Wang, Lucy Dongwei
%A Saito, Mitsuru
%A Sawyer, Andrew
%A Harris, David C H
%A Alexander, Stephen I
%A Durkan, Anne M
%T DEC205-DC targeted DNA vaccines to CX3CR1 and CCL2 are potent and limit macrophage migration.
%B International Journal of Clinical and Experimental Medicine
%D 2012
%C United States
%I E-Century Publishing Corporation
%V 5
%N 1
%P 24-33
%@ 1940-5901
%X Monocytes utilise a variety of chemokines to traffic to atherosclerotic plaques. CX3C chemokine ligand 1 (CX3CL1 & Fractalkine) and its receptor CX3CR1 and monocyte chemoattractant protein 1 (CCL2) have been identified as chemokines/receptors that have an important role in the migration and recruitment of monocytes during the pathogenesis of several inflammatory diseases including atherosclerosis. DNA vectors containing single chain variable region fragment (scFv) for DC-targeted receptor DEC205 were cloned with mouse CX3CR1 and CCL2 genes respectively, and vaccinated into C57/BL6 mice weekly for 3 weeks. Induced anti-CX3CR1 and anti-CCL2 in vaccinated mice was examined by ELISA and Western Blot analysis, while the cellular response was examined by ELISPOT. The inhibition of chemotaxis of J774 macrophages to Py-4-1 endothelial cells was examined by in vitro transwell migration assay using serum collected from vaccinated mice. All vaccinated mice generated anti-CX3CR1 and anti-CCL2 Ab and cellular response by 8 weeks after DNA vaccination. Macrophage migration towards TNF-? activated endothelial cells was significantly inhibited by serum containing both anti-CX3CR1 or anti-CCL2 Ab from vaccinated mice. These results demonstrate that DC-targeting of DNA vaccines to self-antigens generates functional immune responses which can inhibit specific key chemotactic targets. This suggests a potential therapeutic role for chemokine/receptor DNA vaccination in atherosclerosis, where chemotaxis has a pivotal role in the inflammatory process.
%Z FOR Codes: 110704 111601 110705


%0 Journal Article
%~ PubMed
%A Zheng, Dong
%A Cao, Qi
%A Lee, Vincent W S
%A Wang, Ya
%A Zheng, Guoping
%A Wang, Yuanmin
%A Tan, Thian Kui
%A Wang, Changqi
%A Alexander, Stephen I
%A Harris, David C H
%A Wang, Yiping
%T Lipopolysaccharide-pretreated plasmacytoid dendritic cells ameliorate experimental chronic kidney disease.
%B Kidney International
%D 2012
%C United Kingdom, United States
%I Nature Publishing Group
%V 81
%N 9
%P 892-902
%@ 0085-2538
%X Plasmacytoid dendritic cells play important roles in inducing immune tolerance, preventing allograft rejection, and regulating immune responses in both autoimmune disease and graft-versus-host disease. In order to evaluate a possible protective effect of plasmacytoid dendritic cells against renal inflammation and injury, we purified these cells from mouse spleens and adoptively transferred lipopolysaccharide (LPS)-treated cells, modified ex vivo, into mice with adriamycin nephropathy. These LPS-treated cells localized to the kidney cortex and the lymph nodes draining the kidney, and protected the kidney from injury during adriamycin nephropathy. Glomerulosclerosis, tubular atrophy, interstitial expansion, proteinuria, and creatinine clearance were significantly reduced in mice with adriamycin nephropathy subsequently treated with LPS-activated plasmacytoid dendritic cells as compared to the kidney injury in mice given naive plasmacytoid dendritic cells. In addition, LPS-pretreated cells, but not naive plasmacytoid dendritic cells, convert CD4+CD25- T cells into Foxp3+ regulatory T cells and suppress the proinflammatory cytokine production of endogenous renal macrophages. This may explain their ability to protect against renal injury in adriamycin nephropathy.Kidney International advance online publication, 8 February 2012; doi:10.1038/ki.2011.471.
%Z FOR Codes: 110704 111601 110707


%0 Journal Article
%~ PubMed
%A Wang, Yuan Min
%A McRae, Jennifer L
%A Robson, Simon C
%A Cowan, Peter J
%A Zhang, Geoff Yu
%A Hu, Min
%A Polhill, Tania
%A Wang, Yiping
%A Zheng, Guoping
%A Wang, Ya
%A Lee, Vincent W S
%A Unwin, Robert J
%A Harris, David C H
%A Dwyer, Karen M
%A Alexander, Stephen I
%T Regulatory T cells participate in CD39-mediated protection from renal injury.
%B European Journal of Immunology
%D 2012
%C Germany
%I Wiley - VCH Verlag GmbH & Co. KGaA
%V 42
%N 9
%P 2441-2451
%@ 0014-2980
%X CD39 is an ecto-enzyme that degrades extracellular nucleotides, such as ATP, and is highly expressed on by the vasculature and circulating cells including Foxp3+ regulatory T (Treg) cells. To study the role of purinergic regulation in renal disease, we used the adriamycin nephropathy (AN) mouse model of chronic renal injury, using human CD39-transgenic (hCD39Tg) and wild-type (WT) BALB/c mice. Effects of CD39 expression by Treg cells were assessed in AN by adoptive transfer of CD4+CD25+ and CD4+CD25- T cells isolated from hCD39Tg and WT. hCD39Tg mice were protected from renal injury in AN with decreased urinary protein and serum creatinine, and significantly less renal injury compared with WT. While WT CD25+ and hCD39Tg CD25- T cells conferred some protection against AN, hCD39Tg CD25+ Treg cells offered greater protection. In vitro studies showed direct pro-apoptotic effects of ATP on renal tubular cells. In conclusion, hCD39 expressed by circulating leukocytes and intrinsic renal cells limits innate AN injury. Specifically CD39 expression by Treg cells contributes to its protective role in renal injury. These findings suggest that extracellular nucleotides mediate AN kidney injury and that CD39, expressed by Treg cells and other cells, is protective in this model.
%Z FOR Codes: 110703


%0 Journal Article
%~ PubMed
%A Lee, Vincent Ws
%A Harris, David Ch
%T Adriamycin nephropathy: A model of focal segmental glomerulosclerosis.
%B Nephrology
%D 2011
%C Australia
%I Wiley-Blackwell Publishing Asia
%V 16
%N 1
%P 30-38
%@ 1440-1797
%X Adriamycin nephropathy (AN) is a rodent model of chronic kidney disease that has been studied extensively and has enabled a greater understanding of the processes underlying the progression of chronic proteinuric renal disease. AN is characterized by podocyte injury followed by glomerulosclerosis, tubulointerstitial inflammation and fibrosis. Genetic studies have demonstrated a number of loci that alter both risk and severity of renal injury induced by Adriamycin. Adriamycin-induced renal injury has been shown in numerous studies to be modulated by both non-immune and immune factors, and has facilitated further study of mechanisms of tubulointerstitial injury. This review will outline the pharmacological behaviour of Adriamycin, and describe in detail the model of AN, including its key structural characteristics, genetic susceptibility and pathogenesis.
%Z FOR Codes: 111699 110704


%0 Journal Article
%~ PubMed
%A Cao, Qi
%A Wang, Changqi
%A Zheng, Dong
%A Wang, Ya
%A Lee, Vincent W S
%A Wang, Yuan Min
%A Zheng, Guoping
%A Tan, Thian Kui
%A Yu, Di
%A Alexander, Stephen I
%A Harris, David C H
%A Wang, Yiping
%T IL-25 Induces M2 Macrophages and Reduces Renal Injury in Proteinuric Kidney Disease.
%B Journal of the American Society of Nephrology : JASN
%D 2011
%C United States
%I Ovid
%V 22
%N 7
%P 1229-39
%@ 1533-3450
%X The kidney contains receptors for the cytokine IL-25, but the effects of IL-25 in CKD are unknown. Here, we induced adriamycin nephropathy in both BALB/c mice and severe combined immunodeficient (SCID) mice, and we injected IL-25 for 7 consecutive days starting at day 5 after adriamycin administration. BALB/c mice treated with IL-25 had less glomerulosclerosis, tubular atrophy, interstitial expansion, and proteinuria than control mice at day 28. IL-25 increased the levels of IL-4 and IL-13 in serum, kidney, renal draining lymph nodes, and CD4+ lymphocytes. IL-25 also directly suppressed effector macrophages in vitro and in vivo and induced alternatively activated (M2) macrophages in vivo. However, in SCID mice and in BALB/c mice treated with IL-4/13-neutralizing antibody, IL-25 failed to protect against renal injury and did not induce M2. In conclusion, IL-25 protects against renal injury in adriamycin nephropathy in mice by, at least in part, inducing Th2 immune responses.
%Z FOR Codes: 110704 110312


%0 Book Section
%A Lee, Vincent
%A Cao, Qi
%A Wang, Yiping
%A Harris, David
%T Role of Macrophages in Renal Injury,
Repair and Regeneration
%B Regenerative Nephrology
%D 2011
%C United Kingdom, Unit
%I Elsevier Inc.
%V 
%N 
%P 125-140
%@ 9780123809285
%E Goligorsky, Michael S.
%X 
%Z FOR Codes: 110312


%0 Journal Article
%~ PubMed
%A Zheng, Dong
%A Wang, Yiping
%A Cao, Qi
%A Lee, Vincent W S
%A Zheng, Guoping
%A Sun, Yan
%A Tan, Thian K
%A Wang, Ya
%A Alexander, Stephen I
%A Harris, David C H
%T Transfused Macrophages Ameliorate Pancreatic and Renal Injury in Murine Diabetes Mellitus.
%B Nephron. Experimental nephrology
%D 2011
%C Switzerland
%I S. Karger AG
%V 118
%N 4
%P e87-99
%@ 1660-2129
%X Alternatively activated macrophages (M2 macrophages) are able to reduce renal injury in murine adriamycin nephropathy. However, the effect of M2 macrophages in other renal diseases such as diabetic nephropathy remains unknown.
%Z FOR Codes: 110704 110299


%0 Journal Article
%~ PubMed
%A Cao, Qi
%A Wang, Yiping
%A Zheng, Dong
%A Sun, Yan
%A Wang, Ya
%A Lee, Vincent W S
%A Zheng, Guoping
%A Tan, Thian Kui
%A Ince, Jon
%A Alexander, Stephen I
%A Harris, David C H
%T IL-10/TGF-{beta}-Modified Macrophages Induce Regulatory T Cells and Protect against Adriamycin Nephrosis.
%B Journal of the American Society of Nephrology : JASN
%D 2010
%C United States
%I American Society of Nephrology
%V 21
%N 6
%P 933-42
%@ 1533-3450
%X IL-10/TGF-beta-modified macrophages, a subset of activated macrophages, produce anti-inflammatory cytokines, suggesting that they may protect against inflammation-mediated injury. Here, macrophages modified ex vivo by IL-10/TGF-beta (IL-10/TGF-beta Mu2) significantly attenuated renal inflammation, structural injury, and functional decline in murine adriamycin nephrosis (AN). These cells deactivated effector macrophages and inhibited CD4+ T cell proliferation. IL-10/TGF-beta Mu2 expressed high levels of the regulatory co-stimulatory molecule B7-H4, induced regulatory T cells from CD4+CD25- T cells in vitro, and increased the number of regulatory T cells in lymph nodes draining the kidneys in AN. The phenotype of IL-10/TGF-beta Mu2 did not switch to that of effector macrophages in the inflamed kidney, and these cells did not promote fibrosis. Taken together, these data demonstrate that IL-10/TGF-beta-modified macrophages effectively protect against renal injury in AN and may become part of a therapeutic strategy for chronic inflammatory disease.
%Z FOR Codes: 110704


%0 Journal Article
%~ PubMed
%A Tan, Thian Kui
%A Zheng, Guoping
%A Hsu, Tzu-Ting
%A Wang, Ying
%A Lee, Vincent W S
%A Tian, Xinrui
%A Wang, Yiping
%A Cao, Qi
%A Wang, Ya
%A Harris, David C H
%T Macrophage Matrix Metalloproteinase-9 Mediates Epithelial-Mesenchymal Transition in Vitro in Murine Renal Tubular Cells.
%B The American journal of pathology
%D 2010
%C United States
%I American Society for Investigative Pathology
%V 176
%N 3
%P 1256-70
%@ 0002-9440
%X As a rich source of pro-fibrogenic growth factors and matrix metalloproteinases (MMPs), macrophages are well-placed to play an important role in renal fibrosis. However, the exact underlying mechanisms and the extent of macrophage involvement are unclear. Tubular cell epithelial-mesenchymal transition (EMT) is an important contributor to renal fibrosis and MMPs to induction of tubular cell EMT. The aim of this study was to investigate the contribution of macrophages and MMPs to induction of tubular cell EMT. The murine C1.1 tubular epithelial cell line and primary tubular epithelial cells were cultured in activated macrophage-conditioned medium (AMCM) derived from lipopolysaccharide-activated J774 macrophages. MMP-9, but not MMP-2 activity was detected in AMCM. AMCM-induced tubular cell EMT in C1.1 cells was inhibited by broad-spectrum MMP inhibitor (GM6001), MMP-2/9 inhibitor, and in AMCM after MMP-9 removal by monoclonal Ab against MMP-9. AMCM-induced EMT in primary tubular epithelial cells was inhibited by MMP-2/9 inhibitor. MMP-9 induced tubular cell EMT in both C1.1 cells and primary tubular epithelial cells. Furthermore, MMP-9 induced tubular cell EMT in C1.1 cells to an extent similar to transforming growth factor-beta. Transforming growth factor-beta-induced tubular cell EMT in C1.1 cells was inhibited by MMP-2/9 inhibitor. Our in vitro study provides evidence that MMPs, specifically MMP-9, secreted by effector macrophages can induce tubular cell EMT and thereby contribute to renal fibrosis.
%Z FOR Codes: 111699


%0 Journal Article
%~ PubMed
%A Lee, Vincent W S
%A Qin, Xiaohong
%A Wang, Yiping
%A Zheng, Guoping
%A Wang, Ya
%A Wang, Ying
%A Ince, Jon
%A Tan, Thian K
%A Kairaitis, Lukas K
%A Alexander, Stephen I
%A Harris, David C H
%T The CD40-CD154 co-stimulation pathway mediates innate immune injury in adriamycin nephrosis.
%B Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
%D 2010
%C United Kingdom, Belg
%I Oxford University Press
%V 25
%N 3
%P 717-30
%@ 1460-2385
%X Blockade of CD40-CD40 ligand (CD154) interactions protects against renal injury in adriamycin nephropathy (AN) in immunocompetent mice. To investigate whether this protection relied on adaptive or cognate immunity, we tested the effect of CD40-CD154 blockade in severe combined immunodeficient (SCID) mice.
%Z FOR Codes: 110701 110707


%0 Book Section
%A Lee, Vincent
%T Acute Renal Failure and Rhabdomyolysis
%B Clinical Cases in Kidney Diseases
%D 2008
%C United States
%I McGraw-Hill Company
%V 
%N 
%P 0
%@ 9780074717806
%E Harris, David
%X 
%Z FOR Codes: 110312


%0 Journal Article
%~ PubMed
%A Wang, Ying
%A Wang, Yiping
%A Cai, Qi
%A Zheng, Guoping
%A Lee, Vincent W S
%A Zheng, Dong
%A Li, Xiaomei
%A Tan, Thian Kui
%A Harris, David C H
%T By Homing to the Kidney, Activated Macrophages Potently Exacerbate Renal Injury.
%B The American journal of pathology
%D 2008
%C United States
%I Amer Soc Investigative Pathology
%V 172
%N 6
%P 1491-9
%@ 1525-2191
%X Macrophages are important mediators of injury in most types of human kidney diseases; however, the pathogenic importance of both macrophage number and activation status is unknown. To examine this question, severe-combined immunodeficient mice with adriamycin nephrosis, an experimental model of human focal segmental glomerulosclerosis, were treated intravenously with either resting (1 x 10(6) to 5 x 10(6)) or activated (1 x 10(3) to 1 x 10(6)) macrophages on day 6 postadriamycin administration, and the effects on kidney injury were examined. On day 28, renal injury was worse in the group that received activated macrophages at doses as low as 1 x 10(4) macrophages per mouse compared with control adriamycin nephrotic mice. However, treatment with resting macrophages at doses as high as 5 x 10(6) macrophages per mouse had no significant effect on either renal histology or function. The transferred activated macrophages homed to inflamed kidneys during the middle-to-late stages of the disease, but such homing was not observed for resting macrophages. This study of in vivo cell adoptive transfer supports the importance of macrophage activation status over macrophage number in causing renal injury. These data suggest that therapeutic strategies for treating progressive kidney diseases should target activated macrophages.
%Z FOR Codes: 110704 111601


%0 Book Section
%A Lee, Vincent
%T Oedema and Nephrotic Syndrome
%B Clinical Cases in Kidney Diseases
%D 2008
%C United States
%I McGraw-Hill Company
%V 
%N 
%P 438-450
%@ 9780074717806
%E Harris, David
%X 
%Z FOR Codes: 110312


%0 Journal Article
%~ PubMed
%A Wang, Yuan Min
%A Hu, Min
%A Wang, Ya
%A Polhill, Tania
%A Zhang, Geoff Yu
%A Wang, Yiping
%A Lee, Vincent W S
%A Harris, David C H
%A Alexander, Stephen I
%T Regulatory T cells in renal disease.
%B International Journal of Clinical and Experimental Medicine
%D 2008
%C United States
%I E-Century Publishing
%V 1
%N 4
%P 294-304
%@ 1940-5901
%X Regulatory T cells (Tregs) have a key role in immune homeostasis and in suppressing unwanted inflammatory responses toward self-antigens. Tregs have been implicated in the control of initial activation events, and play roles in limiting proliferation, differentiation and effector functions of T helper cells. However, the activities of Tregs in the development and progression of kidney disease are not fully elucidated. We have demonstrated the potency of Tregs in animal models of kidney disease. In this review, we summarise mechanistic information from rodent models on the roles of Tregs in glomerular immunopathology and discuss the function of Tregs in diverse kidney diseases. Further studies of Tregs should provide important insights into designing of therapeutic strategies to prevent human kidney disease.
%Z FOR Codes: 110704 110312 111601


%0 Journal Article
%~ PubMed
%A Lee, Vincent Weng Seng
%A Wang, Yuan Min
%A Wang, Yiping
%A Zheng, Dong
%A Polhill, Tania
%A Cao, Qi
%A Wu, Huiling
%A Alexander, Ian
%A Alexander, Stephen
%A Harris, David
%T Regulatory immune cells in kidney disease
%B American journal of physiology. Renal physiology
%D 2008
%C United States
%I American Physiological Society
%V 295
%N 2
%P F335-42
%@ 0363-6127
%X Lymphocytes and macrophages act as effector immune cells in the initiation and progression of renal injury. Recent data have shown that subpopulations of these immune cells (regulatory T lymphocytes and alternately-activated or regulatory macrophages) are potent modulators of tissue injury and repair in renal disease. Recent animal studies examining the therapeutic effect of these cells raise the exciting possibility that strategies targeting these cell types may be effective in treating and preventing kidney disease in humans. This review will describe their biological role in experimental kidney disease and therapeutic potential in clinical nephrology.
%Z FOR Codes: 110704


%0 Journal Article
%~ PubMed
%A Wang, Y
%A Wang, Y P
%A Zheng, G
%A Lee, V W S
%A Ouyang, L
%A Chang, D H H
%A Mahajan, D
%A Coombs, J
%A Wang, Y M
%A Alexander, S I
%A Harris, D C H
%T Ex vivo programmed macrophages ameliorate experimental chronic inflammatory renal disease.
%B Kidney international
%D 2007
%C United States
%I Blackwell Publishing, Inc.
%V 72
%N 3
%P 290-9
%@ 1523-1755
%X Macrophage infiltration of the kidney is a prominent feature associated with the severity of renal injury and progressive renal failure. To determine the influence of macrophages in renal disease models in the absence of endogenous T and B cells, we performed adoptive transfer of macrophages into severe combined immunodeficient (SCID) mice. In this study, macrophages were isolated from the spleens of BALB/c mice and stimulated with lipopolysaccharide to induce classically activated M1 macrophages or with interleukin-4 (IL-4) and IL-13 to induce alternatively activated M2 macrophages. These macrophages were then infused into SCID mice with adriamycin nephropathy; an in vivo model of chronic inflammatory renal disease analogous to human focal segmental glomerulosclerosis. Mice infused with M1 macrophages had a more severe histological and functional injury, whereas M2 macrophage-induced transfused mice had reduced histological and functional injury. Both M1 and M2 macrophages localized preferentially to the area of injury and maintained their phenotypes even after 4 weeks. The protective effect of M2 macrophages was associated with reduced accumulation and possibly downregulated chemokine and inflammatory cytokine expression of the host infiltrating macrophages. Our findings demonstrate that macrophages not only act as effectors of immune injury but can be induced to provide protection against immune injury.
%Z FOR Codes: