Tissue‐resident macrophages — how to humanize our knowledge

Schlitzer, Andreas; Schultze, Joachim L.

doi:10.1038/icb.2016.82

Cited by 16 publications

(12 citation statements)

References 72 publications

(145 reference statements)

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“…Interestingly, unlike in mice, the expression of CD64 and MerTK was higher in the CD14 hi CD11b hi subset (Fig. S6B ) 40 , 42 resembling human dermal CD14 + tissue-resident monocyte-derived macrophages that express CD64 42 . CD11b int CD11c lo-neg Mϕ were CD14 lo and thus appear to phenotypically resemble KRM (Fig.…”

Section: Resultsmentioning

confidence: 90%

“…To assess the potential clinical relevance of our findings we initially identified macrophages by flow cytometry in the unaffected portion of a human kidney removed due to renal cell carcinoma. We used a combination of conventional markers like CD68, HLA-DR, CD11b, CD11c, CD14, CD16, and the additional markers CD64 and MerTK 12 , 40 . Macrophages were classified as Lineage neg CD45 + HLA-DR + CD68 + and CD11b + CD14 + but CD16 lo-neg , indicating a blood-derived origin 5 , 33 , 41 .…”

Section: Resultsmentioning

confidence: 99%

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Kidney-resident macrophages promote a proangiogenic environment in the normal and chronically ischemic mouse kidney

Puranik

Leaf

Jensen

et al. 2018

Sci Rep

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Renal artery stenosis (RAS) caused by narrowing of arteries is characterized by microvascular damage. Macrophages are implicated in repair and injury, but the specific populations responsible for these divergent roles have not been identified. Here, we characterized murine kidney F4/80+CD64+ macrophages in three transcriptionally unique populations. Using fate-mapping and parabiosis studies, we demonstrate that CD11b/cint are long-lived kidney-resident (KRM) while CD11chiMϕ, CD11cloMϕ are monocyte-derived macrophages. In a murine model of RAS, KRM self-renewed, while CD11chiMϕ and CD11cloMϕ increased significantly, which was associated with loss of peritubular capillaries. Replacing the native KRM with monocyte-derived KRM using liposomal clodronate and bone marrow transplantation followed by RAS, amplified loss of peritubular capillaries. To further elucidate the nature of interactions between KRM and peritubular endothelial cells, we performed RNA-sequencing on flow-sorted macrophages from Sham and RAS kidneys. KRM showed a prominent activation pattern in RAS with significant enrichment in reparative pathways, like angiogenesis and wound healing. In culture, KRM increased proliferation of renal peritubular endothelial cells implying direct pro-angiogenic properties. Human homologs of KRM identified as CD11bintCD11cintCD68+ increased in post-stenotic kidney biopsies from RAS patients compared to healthy human kidneys, and inversely correlated to kidney function. Thus, KRM may play protective roles in stenotic kidney injury through expansion and upregulation of pro-angiogenic pathways.

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Section: Resultsmentioning

confidence: 90%

Section: Resultsmentioning

confidence: 99%

Kidney-resident macrophages promote a proangiogenic environment in the normal and chronically ischemic mouse kidney

Puranik

Leaf

Jensen

et al. 2018

Sci Rep

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“…(115) At present, comparative studies on human versus mouse liver macrophage subsets are limited, although many key aspects of resident KC versus recruited MoMF, activation and recruitment signals, and metabolic activities appear to be conserved. (39,60,133,134) The liver microenvironment is also different between mouse models and human disease, and several studies have attempted to tackle species differences by using humanized livers. However, such studies currently require the mice to be immune deficient (e.g., severe combined immunodeficient [SCID] mice), thus limiting the ability to study macrophages in the context of a normal immune environment.…”

Section: Translational Research: From Mouse Models To Human Diseasesmentioning

confidence: 99%

Liver Macrophages: Old Dogmas and New Insights

2019

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Inflammation is a hallmark of virtually all liver diseases, such as liver cancer, fibrosis, nonalcoholic steatohepatitis, alcoholic liver disease, and cholangiopathies. Liver macrophages have been thoroughly studied in human disease and mouse models, unravelling that the hepatic mononuclear phagocyte system is more versatile and complex than previously believed. Liver macrophages mainly consist of liver-resident phagocytes, or Kupffer cells (KCs), and bone marrow-derived recruited monocytes. Although both cell populations in the liver demonstrate principal functions of macrophages, such as phagocytosis, danger signal recognition, cytokine release, antigen processing, and the ability to orchestrate immune responses, KCs and recruited monocytes retain characteristic ontogeny markers and remain remarkably distinct on several functional aspects. While KCs dominate the hepatic macrophage pool in homeostasis ("sentinel function"), monocyte-derived macrophages prevail in acute or chronic injury ("emergency response team"), making them an interesting target for novel therapeutic approaches in liver disease. In addition, recent data acquired by unbiased large-scale techniques, such as single-cell RNA sequencing, unraveled a previously unrecognized complexity of human and murine macrophage polarization abilities, far beyond the old dogma of inflammatory (M1) and anti-inflammatory (M2) macrophages. Despite tremendous progress, numerous challenges remain in deciphering the full spectrum of macrophage activation and its implication in either promoting liver disease progression or repairing injured liver tissue. Being aware of such heterogeneity in cell origin and function is of crucial importance when studying liver diseases, developing novel therapeutic interventions, defining macrophage-based prognostic biomarkers, or designing clinical trials. Growing knowledge in gene expression modulation and emerging technologies in drug delivery may soon allow shaping macrophage populations toward orchestrating beneficial rather than detrimental inflammatory responses. (Hepatology Communications 2019;3:730-743). T he liver is the largest solid organ and exerts vital metabolic functions. Liver diseases leading to liver cirrhosis or cancer are increasingly challenging for public health, the current trend being an augmentation of such diseases mainly caused by changes in alimentation and life habits. (1) Liver diseases are various by nature in terms of etiologies, chronicity, and chances of recovery. However, one constant feature is the presence of liver inflammation, and most remarkably, there is an apparent compulsory association of inflammation with a poor outcome for patients. (2-6) Liver macrophages are included in the mononuclear phagocyte system and are renown cornerstones in most if not all inflammation-related liver disorders due to their ability to respond to a seemingly infinite

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“…Tissues‐resident macrophages (such as microglia in the brain, Kupffer cells in the liver, and osteoclasts in bones) are found in connective tissues and in every organ in the body. They are highly specialized, exhibiting physiological roles adapted to the biology of the hosting tissue . Accordingly, tissue‐resident macrophages exhibit specific transcriptional and metabolic programs which are specific to the tissue residence .…”

Section: Functional Plasticity One Of the Most Remarkable Propertiesmentioning

confidence: 99%

The roles of CSFs on the functional polarization of tumor‐associated macrophages

et al. 2017

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Macrophages have a central role in numerous physiological processes, such as immune defense, maintenance of tissue homeostasis, wound healing, and inflammation. Moreover, in numerous severe disorders, such as cancer or chronic inflammation, their functions can be profoundly affected. Macrophages continuously sense their environment and adapt their phenotypes and functions to the local requirements; this process is called plasticity. In addition to stress signals, metabolites, and direct cell‐contact interactions with surrounding cells, numerous cytokines play a central role in controlling macrophage polarization. In this review, we will focus on three human macrophage differentiation factors: macrophage colony‐stimulating factor (M‐CSF), IL‐34, and granulocyte M‐CSF. These CSFs allow human monocyte survival, promote their differentiation into macrophages, and control macrophage polarization as they give rise to cells with different phenotype and functions. Based on recent observations, the role of granulocyte CSF on macrophage polarization is also addressed. Finally, our current knowledge on the expression of these growth factors in tumor microenvironment and their impact on the generation and polarization of tumor‐associated macrophages are summarized.

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Tissue‐resident macrophages — how to humanize our knowledge

Cited by 16 publications

References 72 publications

Kidney-resident macrophages promote a proangiogenic environment in the normal and chronically ischemic mouse kidney

Kidney-resident macrophages promote a proangiogenic environment in the normal and chronically ischemic mouse kidney

Liver Macrophages: Old Dogmas and New Insights

The roles of CSFs on the functional polarization of tumor‐associated macrophages

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