The immune system and kidney disease: basic concepts and clinical implications

Kurts, Christian; Panzer, Ulf; Anders, Hans‐Joachim; Rees, Andrew J.

doi:10.1038/nri3523

Cited by 555 publications

(569 citation statements)

References 154 publications

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“…Different leukocyte subsets contribute to renal fibrosis in native kidneys (23,(28)(29)(30), in particular professional phagocytic and antigen-presenting cells, such as renal resident and infiltrating macrophages and dendritic cells. These cells exhibit a remarkable phenotypic plasticity and functional overlap.…”

Section: The Role Of Immune Cellsmentioning

confidence: 99%

“…They exert various functions depending on their phenotype and pathological context which can result in proor anti-fibrotic effects or have no effects at all (23,(31)(32)(33)(34)(35)(36)(37)(38)(39)(40). Apart from a number of chemokines driving their influx and activation such as CX3CR1 (28,30,31,41), several molecules also play an important role including galectin-3 (42,43), the receptor for macrophage colony-stimulating factor (44), the Wnt pathway ligand Wnt7b (45) and interleukin 10 (46).…”

Section: The Role Of Immune Cellsmentioning

confidence: 99%

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Renal Allograft Fibrosis: Biology and Therapeutic Targets

Floege

2015

American Journal of Transplantation

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Section: The Role Of Immune Cellsmentioning

confidence: 99%

Section: The Role Of Immune Cellsmentioning

confidence: 99%

Renal Allograft Fibrosis: Biology and Therapeutic Targets

Floege

2015

American Journal of Transplantation

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“…However, if dysregulated, it can also cause significant tissue injury. Inappropriate recruitment and activation of neutrophils are recognized as major contributors to organ damage in numerous inflammatory diseases, including inflammatory arthritis, acute respiratory distress syndrome, systemic lupus erythematosus, and acute glomerulonephritis (1)(2)(3)(4). Although our understanding of the molecular basis of neutrophil recruitment is well-developed, less is known about the interactions of neutrophils with other circulating immune cells during the development of the innate inflammatory response.…”

mentioning

confidence: 99%

“…The glomerulus in the kidney is a key target of damaging inflammation in a wide range of conditions (2). Indeed, glomerulonephritis is a leading cause of end-stage renal failure.…”

mentioning

confidence: 99%

Patrolling monocytes promote intravascular neutrophil activation and glomerular injury in the acutely inflamed glomerulus

Finsterbusch

Hall

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

100

139

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Nonclassical monocytes undergo intravascular patrolling in blood vessels, positioning them ideally to coordinate responses to inflammatory stimuli. Under some circumstances, the actions of monocytes have been shown to involve promotion of neutrophil recruitment. However, the mechanisms whereby patrolling monocytes control the actions of neutrophils in the circulation are unclear. Here, we examined the contributions of monocytes to antibody-and neutrophildependent inflammation in a model of in situ immune complexmediated glomerulonephritis. Multiphoton and spinning disk confocal intravital microscopy revealed that monocytes patrol both uninflamed and inflamed glomeruli using β 2 and α 4 integrins and CX 3 CR1. Monocyte depletion reduced glomerular injury, demonstrating that these cells promote inappropriate inflammation in this setting. Monocyte depletion also resulted in reductions in neutrophil recruitment and dwell time in glomerular capillaries and in reactive oxygen species (ROS) generation by neutrophils, suggesting a role for cross-talk between monocytes and neutrophils in induction of glomerulonephritis. Consistent with this hypothesis, patrolling monocytes and neutrophils underwent prolonged interactions in glomerular capillaries, with the duration of these interactions increasing during inflammation. Moreover, neutrophils that interacted with monocytes showed increased retention and a greater propensity for ROS generation in the glomerulus. Also, renal patrolling monocytes, but not neutrophils, produced TNF during inflammation, and TNF inhibition reduced neutrophil dwell time and ROS production, as well as renal injury. These findings show that monocytes and neutrophils undergo interactions within the glomerular microvasculature. Moreover, evidence indicates that, in response to an inflammatory stimulus, these interactions allow monocytes to promote neutrophil recruitment and activation within the glomerular microvasculature, leading to neutrophil-dependent tissue injury.monocyte-neutrophil interaction | inflammation | glomerulonephritis | reactive oxygen species | tumor necrosis factor N eutrophil recruitment is a crucial event in the response to tissue injury and host defense against pathogens. However, if dysregulated, it can also cause significant tissue injury. Inappropriate recruitment and activation of neutrophils are recognized as major contributors to organ damage in numerous inflammatory diseases, including inflammatory arthritis, acute respiratory distress syndrome, systemic lupus erythematosus, and acute glomerulonephritis (1-4). Although our understanding of the molecular basis of neutrophil recruitment is well-developed, less is known about the interactions of neutrophils with other circulating immune cells during the development of the innate inflammatory response. However, over the last decade, evidence has emerged that neutrophil recruitment and function during inflammation can be influenced by another circulating immune cell-the monocyte (5-10).Monocytes exist in two major populations,...

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“…T he renal mononuclear phagocyte system consists of an extensive network of mononuclear phagocytes (i.e., dendritic cells [DCs] and macrophages) (1,2). Although there is no clear demarcation between these cell types, DCs are typically specialized at regulating other immune effector cells, especially T cells, whereas macrophages preferentially act as immune effectors in innate immune responses or contribute to tissue repair (3)(4)(5)(6).…”

mentioning

confidence: 99%

CX3CR1 Reduces Kidney Fibrosis by Inhibiting Local Proliferation of Profibrotic Macrophages

Engel

Krause

Snelgrove

et al. 2015

The Journal of Immunology

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A dense network of macrophages and dendritic cells (DC) expressing the chemokine receptor CX3CR1 populates most tissues. We recently reported that CX3CR1 regulates the abundance of CD11c+ DC in the kidney and thereby promotes renal inflammation in glomerulonephritis. Given that chronic inflammation usually causes fibrosis, we hypothesized that CX3CR1 deficiency should attenuate renal fibrosis. However, when we tested this hypothesis using the DC-independent murine fibrosis model of unilateral ureteral obstruction, kidney fibrosis was unexpectedly more severe, despite less intrarenal inflammation. Two-photon imaging and flow cytometry revealed in kidneys of CX3CR1-deficient mice more motile Ly6C/Gr-1+ macrophages. Flow cytometry verified that renal macrophages were more abundant in the absence of CX3CR1 and produced more of the key profibrotic mediator, TGF-β. Macrophages accumulated because of higher intrarenal proliferation, despite reduced monocyte recruitment and higher signs of apoptosis within the kidney. These findings support the theory that tissue macrophage numbers are regulated through local proliferation and identify CX3CR1 as a regulator of such proliferation. Thus, CX3CR1 inhibition should be avoided in DC-independent inflammatory diseases because it may promote fibrosis.

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The immune system and kidney disease: basic concepts and clinical implications

Cited by 555 publications

References 154 publications

Renal Allograft Fibrosis: Biology and Therapeutic Targets

Renal Allograft Fibrosis: Biology and Therapeutic Targets

Patrolling monocytes promote intravascular neutrophil activation and glomerular injury in the acutely inflamed glomerulus

CX3CR1 Reduces Kidney Fibrosis by Inhibiting Local Proliferation of Profibrotic Macrophages

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