Adoptive transfer of macrophages ameliorates renal fibrosis in mice

Nishida, Masashi; Okumura, Yasuko; Fujimoto, Shinichiro; Shiraishi, Isao; Itoi, Toshiyuki; Hamaoka, Kenji

doi:10.1016/j.bbrc.2005.04.083

Cited by 79 publications

(64 citation statements)

References 12 publications

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“…Alternatively activated macrophage subsets induced by Th2 cytokines, immune complexes, or TGF-b/IL-10 treatment have proven efficacy in suppressing murine chemically induced colitis, experimental autoimmune encephalomyelitis, and kidney diseases (19)(20)(21)(22)(23). Our study shows that AvCystatin-Mregs acquire a phenotype characterized by the combined expression of markers assigned previously to the M2a and M2b subsets (34), reflecting the broad spectrum of macrophage activation as recently shown by Xue et al (37).…”

Section: Discussionsupporting

confidence: 82%

“…Cell-based therapies constitute a promising approach in which cells are differentiated into an immunosuppressive or regulatory phenotype and administered into patients. Experimentally, macrophages have been evaluated as good candidates for cell-based therapeutic intervention not only for atopic and autoimmune diseases, but also for the treatment of kidney diseases (18)(19)(20)(21)(22)(23)(24). Furthermore, regulatory macrophages have been successfully applied to human transplantation patients in first clinical trials to interfere with overt immune responses (25,26) and are discussed as a future therapy in solid-organ transplantation and beyond (27).…”

Section: Discussionmentioning

confidence: 99%

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A Novel Regulatory Macrophage Induced by a Helminth Molecule Instructs IL-10 in CD4+ T Cells and Protects against Mucosal Inflammation

Ziegler

Rausch

Steinfelder

et al. 2015

The Journal of Immunology

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Immunomodulation is a common feature of chronic helminth infections and mainly attributed to the secretion of bioactive molecules, which target and modify host immune cells. In this study, we show that the helminth immunomodulator AvCystatin, a cysteine protease inhibitor, induces a novel regulatory macrophage (Mreg; AvCystatin-Mreg), which is sufficient to mitigate major parameters of allergic airway inflammation and colitis in mice. A single adoptive transfer of AvCystatin-Mreg before allergen challenge suppressed allergen-specific IgE levels, the influx of eosinophils into the airways, local and systemic Th2 cytokine levels, and mucus production in lung bronchioles of mice, whereas increasing local and systemic IL-10 production by CD4+ T cells. Moreover, a single administration of AvCystatin-Mreg during experimentally induced colitis strikingly reduced intestinal pathology. Phenotyping of AvCystatin-Mreg revealed increased expression of a distinct group of genes including LIGHT, sphingosine kinase 1, CCL1, arginase-1, and costimulatory molecules, CD16/32, ICAM-1, as well as PD-L1 and PD-L2. In cocultures with dendritic cells and CD4+ T cells, AvCystatin-Mreg strongly induced the production of IL-10 in a cell-contact–independent manner. Collectively, our data identify a specific suppressive macrophage population induced by a single parasite immunomodulator, which protects against mucosal inflammation.

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Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 99%

A Novel Regulatory Macrophage Induced by a Helminth Molecule Instructs IL-10 in CD4+ T Cells and Protects against Mucosal Inflammation

Ziegler

Rausch

Steinfelder

et al. 2015

The Journal of Immunology

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“…[35][36][37] Macrophage depletion attenuated fibrosis in a unilateral ureteral obstruction (UUO) model of injury, suggesting that macrophage infiltration may be deleterious. 38 Imatinib-treated monocyte/macrophages in vitro had reduced proliferation in response to macrophage colony stimulating factor. 9 This finding was attributed to imatinib's inhibitory effect on the phosphorylation of c-fms, the receptor for macrophage colony-stimulating factor.…”

Section: Monocytes Macrophages and Dendritic Cellsmentioning

confidence: 98%

Imatinib

Wallace

Gewin

2013

Journal of the American Society of Nephrology

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The treatments for many autoimmune diseases are limited in efficacy, and long-term use is associated with severe adverse events. The tyrosine kinase inhibitors have proven to be well tolerated for long treatment periods, with minimal adverse events, in the oncology population. These agents have recently been used to treat autoimmune diseases. We review the potential mechanisms whereby tyrosine kinase inhibitors may modulate the immune response and inhibit fibrogenesis and discuss the current evidence for their use in the treatment of autoimmune diseases of the kidney.

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“…Furthermore, ex vivo manipulation of macrophages using specific cytokines confirmed that classically activated, M1 macrophages worsen chronic inflammatory adriamycin nephropathy, whereas alternatively activated M2 macrophages reduce histological disruption and functional injury [36]. Of note, in the heart Camargo et al [37] have [39] Glycerol-induced ARF (mouse) MSCs Enhanced tubular proliferation [68] IR (rat) Papilla LRCs Proliferation and incorporation [149] IR (mouse) Bone marrow No functional improvement, intrarenal cells are the main source of repopulating cell during repair [22] Folic acid-induced acute tubular injury (mouse) Bone marrow Intrinsic tubular cell proliferation accounts for repair after damage [150] Folic acid-induced acute tubular injury (mouse) Bone marrow 10% incorporation in tubules and G-CSF doubles this rate [151] IR (rat) MSCs Improved renal function and less injury [152] Cisplatin-induced renal failure (mouse) MSCs Accelerated tubular proliferation [153] UUO (mouse) Bone marrow macrophages Reduced renal fibrosis [41] IR (rat) MSCs Improved renal function, increased proliferation and decreased apoptosis [84] IR (rat) rKS56 (S3 segment outgrowth) Replace tubular and improve function [80] Glycerol-induced tubulonecrosis (mouse) Human CD133 + cells Homing and tubular integration [66] UUO (rat) Label-retaining cells (LRC) Proliferates, migrates and transdifferentiates into fibroblast-like cells [27] Cisplatin-induced renal failure (mouse) G-CSF ± M-CSF Improvement in renal function and prevention of renal tubular injury [154] Anti-Thy1.1 GN (rat) MSCs Increased glomerular proliferation and reduction in proteinuria [53] Col4α3 deficiency (mouse) MSCs Prevented loss of peritubular capillaries and reduced fibrosis but no increase in function or survival [24] Col4α3 deficiency (mouse) Bone marrow Partial restoration of expression of the type IV collagen α3 chain, improved histology and function [25] Col4α3 deficiency (mouse) MSCs Improved function and glomerular scarring and interstitial fibrosis reduced [155] UUO (mouse) BM Instertitial BM-derived cells do not contribute significantly to collagen synthesis after damage [74] Adriamycin-nephropathy (mouse) Renal side population Functional amprovement but very low rate of engraftment. [78] IR (rat) Multipotent renal progenitor cells In vivo epithelial differentiation, no difference on renal function [67] Cultured met...…”

Section: Bone Marrow-derived Cellsmentioning

confidence: 99%

Stem cell options for kidney disease

Hopkins

Rae

et al. 2008

The Journal of Pathology

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Chronic kidney disease (CKD) is increasing at the rate of 6-8% per annum in the US alone. At present, dialysis and transplantation remain the only treatment options. However, there is hope that stem cells and regenerative medicine may provide additional regenerative options for kidney disease. Such new treatments might involve induction of repair using endogenous or exogenous stem cells or the reprogramming of the organ to reinitiate development. This review addresses the current state of understanding with respect to the ability of non-renal stem cell sources to influence renal repair, the existence of endogenous renal stem cells and the biology of normal renal repair in response to damage. Understanding repair options via an understanding of renal developmentThe prevalence and incidence of chronic kidney disease (CKD) is increasing at 6-8% per annum in the USA alone, largely as a result of increased prevalence of diabetes and obesity [1]. To understand what might be possible with respect to cellular therapies or regenerative medicine for the kidney, one first needs to consider what is understood about normal renal development and response to injury. The kidney has been classically regarded as an organ with minimal cellular turnover and no capacity for regeneration. The subsequent identification of stem cells in a number of such organs, including the brain, has challenged this view. However, the dogma remains that the kidney reaches a maximal complement of nephrons and then loses these over time [2]. This dogma is drawn from our understanding of the development of this organ. The progenitor population during developmentThe kidney is mesodermal in origin and develops from two populations derived from intermediate mesoderm, the ureteric bud (UB) and the metanephric mesenchyme (MM). While an even broader potential had been proposed [3], genetic and lineage analyses have confirmed that the MM gives rise to all portions of the nephron other than the collecting ducts and also gives rise to elements of the renal interstitium [4][5][6]. The UB gives rise to the ureter and collecting ducts only. The MM is apparently not homogeneous but forms condensed mesenchyme around the tips of the branching UB. This cap mesenchyme (CM) contains self-renewing progenitors capable of generating all cells of the nephron other than the collecting ducts via an initial mesenchyme-epithelial transition (MET) event throughout the prenatal developmental period [6]. The continued expression of the transcription factor Six2 in CM is required for maintenance of this stem cell population during kidney development [5]. As the UB branches and extends through the MM, individual MET events occur at the underside of each tip to form a new nephron [2]. This nephron endowment therefore proceeds from the centre of the kidney out to the periphery, with the CM stem cell field remaining on the outer edge of the expanding organ. Endowment of new nephrons is restricted to prenatal development in humans, while in rodents it persists only until the imm...

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Adoptive transfer of macrophages ameliorates renal fibrosis in mice

Cited by 79 publications

References 12 publications

A Novel Regulatory Macrophage Induced by a Helminth Molecule Instructs IL-10 in CD4+ T Cells and Protects against Mucosal Inflammation

A Novel Regulatory Macrophage Induced by a Helminth Molecule Instructs IL-10 in CD4+ T Cells and Protects against Mucosal Inflammation

Imatinib

Stem cell options for kidney disease

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