Resident macrophages reprogram toward a developmental state after acute kidney injury

Lever, Jeremie M.; Hull, Travis D.; Boddu, Ravindra; Pepin, Mark E; Black, Laurence M.; Adedoyin, Oreoluwa O.; Yang, Zhonghai; Traylor, Amie M.; Jiang, Yanlin; Li, Zhang; Peabody, Jacelyn E.; Eckenrode, Han E.; Crossman, David K.; Crowley, Michael R.; Bolisetty, Subhashini; Zimmerman, Kurt A.; Wende, Adam R.; Mrug, Michal; Yoder, Bradley K.; Agarwal, Anupam; George, James F.

doi:10.1172/jci.insight.125503

Cited by 79 publications

(84 citation statements)

References 76 publications

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“…Neutrophils are the most abundant type of granulocytes and make up 40–70% of all white blood cells in humans. They are also the most abundant leukocytes infiltrating the kidney immediately after IRI [ 37 ]. Neutrophils produce and secrete cytotoxic compounds such as reactive oxygen species, while adhering to the endothelium and extravagating into the affected renal tissue.…”

Section: The Differences In Innate Immunity Among Rodents Large Animmentioning

confidence: 99%

Large animal models for translational research in acute kidney injury

et al. 2020

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While extensive research using animal models has improved the understanding of acute kidney injury (AKI), this knowledge has not been translated into effective treatments. Many promising interventions for AKI identified in mice and rats have not been validated in subsequent clinical trials. As a result, the mortality rate of AKI patients remains high. Inflammation plays a fundamental role in the pathogenesis of AKI, and one reason for the failure to translate promising therapeutics may lie in the profound difference between the immune systems of rodents and humans. The immune systems of large animals such as swine, nonhuman primates, sheep, dogs and cats, more closely resemble the human immune system. Therefore, in the absence of a basic understanding of the pathophysiology of human AKI, large animals are attractive models to test novel interventions. However, there is a lack of reviews on large animal models for AKI in the literature. In this review, we will first highlight differences in innate and adaptive immunities among rodents, large animals, and humans in relation to AKI. After illustrating the potential merits of large animals in testing therapies for AKI, we will summarize the current state of the evidence in terms of what therapeutics have been tested in large animal models. The aim of this review is not to suggest that murine models are not valid to study AKI. Instead, our objective is to demonstrate that large animal models can serve as valuable and complementary tools in translating potential therapeutics into clinical practice.

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Section: The Differences In Innate Immunity Among Rodents Large Animmentioning

confidence: 99%

Large animal models for translational research in acute kidney injury

et al. 2020

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“…15,17 Classically, CSF-1 is known to promote macrophage differentiation from bone marrow precursors. 18,19 Tissue resident macrophages and bone marrow-derived mononuclear phagocytes, suggested to be of independent cellular origin, 20 may both produce and respond to CSF-1. 15 Mononuclear phagocytes are a group of cell types including monocytes, macrophages, and dendritic cells (DCs).…”

Section: Colony Stimulating Factor-1 (Csf-1)mentioning

confidence: 99%

“…57,[95][96][97][98] Stamatiades identified F4/80 Hi -expressing cells as predominantly macrophages due to their sessile state, endocytic function, and expression of MerTK, FCGR1, and FCGR4, 96,99 and these conclusions have been confirmed by subsequent studies. 20,98 Macrophages were proposed to produce Wnt7b in a post-injury response that promoted tissue regeneration. 100 However, it is evident that Wnt7b is not the only Wnt ligand produced by myeloid inflammatory cells in the kidney.…”

Section: Cellsmentioning

confidence: 99%

“…100 We recently found that Wnt4 was the most highly expressed Wnt ligand by kidney resident macrophages 6 days after AKI. 20 DCs represent a rare cell type in the healthy kidney and are characterized by the F4/80 Low CD11c Hi surface phenotype, MHCII expression in naive DC, and demonstrate expression of transcription factors Zbtb46 and Batf3. 101,102 Evidence suggests an important role for intrarenal DC in glomerulonephritis.…”

Section: Cellsmentioning

confidence: 99%

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Renal Inflammation and Fibrosis: A Double-edged Sword

Black

Lever

Agarwal

2019

J Histochem Cytochem.

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100

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Renal tissue injury initiates inflammatory and fibrotic processes that occur to promote regeneration and repair. After renal injury, damaged tissue releases cytokines and chemokines, which stimulate activation and infiltration of inflammatory cells to the kidney. Normal tissue repair processes occur simultaneously with activation of myofibroblasts, collagen deposition, and wound healing responses; however, prolonged activation of pro-inflammatory and pro-fibrotic cell types causes excess extracellular matrix deposition. This review focuses on the physiological and pathophysiological roles of specialized cell types, cytokines/chemokines, and growth factors, and their implications in recovery or exacerbation of acute kidney injury.

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“…They exert unique functions depending on their anatomical locations; monitoring and clearing immune complexes is a function of cortical macrophages while bacterial immunity is the responsibility of medullary macrophages [15, 16]. Renal macrophages critically control renal inflammation and tissue remodeling after injury with robust phenotypic reprogramming [19]. Despite the importance of these roles, little is known about how the proportion and distribution of macrophages of different ontogeny change over time in the normal kidney and whether this influences the increased susceptibility and poorer outcomes of older patients to acute and chronic kidney diseases [20-22].…”

mentioning

confidence: 99%

Yolk-Sac-Derived Macrophages Progressively Expand in the Mouse Kidney with Age

Ide

Yahara

Kobayashi

et al. 2019

Preprint

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AbstractRenal macrophages represent a highly heterogeneous and specialized population of myeloid cells with mixed developmental origins from the yolk-sac and hematopoietic stem cells (HSC). They promote both injury and repair by regulating inflammation, angiogenesis, and tissue remodeling. Recent reports highlight differential roles for ontogenically distinct renal macrophage populations in disease. However, little is known about how these populations change over time in normal, uninjured kidneys. Prior reports demonstrated a high proportion of HSC-derived macrophages in the young adult kidney. Unexpectedly, using genetic fate-mapping and parabiosis studies, we find that yolk-sac-derived macrophages progressively expand in number with age and become a major contributor to the renal macrophage population in older mice. This chronological shift in macrophage composition involves cellular proliferation and recruitment from circulating progenitors and may contribute to the distinct immune responses, limited reparative capacity, and increased disease susceptibility of kidneys in the elderly population.

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Resident macrophages reprogram toward a developmental state after acute kidney injury

Abstract: Conflict of interest: MM reports grants and consulting fees from Otsuka Pharmaceutical and Sanofi. AA serves as a consultant for DynaMed and is on the advisory board of Goldilocks Therapeutics.

Cited by 79 publications

References 76 publications

Large animal models for translational research in acute kidney injury

Large animal models for translational research in acute kidney injury

Renal Inflammation and Fibrosis: A Double-edged Sword

Yolk-Sac-Derived Macrophages Progressively Expand in the Mouse Kidney with Age

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