Macrophages in health and disease

Park, Matthew D.; Silvin, Aymeric; Ginhoux, Florent; Mérad, Miriam

doi:10.1016/j.cell.2022.10.007

Cited by 271 publications

(175 citation statements)

References 249 publications

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“…For instance, SPP1+ macrophage recruitment to the fatty liver from circulating monocytes coincides with the lack of Kupffer cells [50]. Hence the fine balance between tissue repair and fibrosis, could be explained by these spatiotemporally regulated infiltrating monocytes and their differentiation state (homeostatic/repair vs inflammatory/pro-fibrotic) within the tissue microenvironment [107]. Our results Aging is characterized by low grade inflammation, and here we report an association of MAMs in aged heart and lung in humans, which we replicated using separate murine models of aging.…”

Section: Discussionmentioning

confidence: 99%

“…Our trajectory analysis extends this observation to six different human tissues, adding further resolution to the SPP1+ macrophages. According to the continuum model of monocyte-to-macrophage differentiation (or activation paths [106]), a healthy tissue environment is maintained by environmental cues and the ability of the monocyte-derived macrophages to undergo homeostatic differentiation into tissue resident macrophages [107]. The disease state is accompanied by monocyte-derived macrophages infiltrating tissues, and progressively losing the ability to support tissue resident macrophages because of the pathologically evolving environmental cues [107].…”

Section: Discussionmentioning

confidence: 99%

“…According to the continuum model of monocyte-to-macrophage differentiation (or activation paths [106]), a healthy tissue environment is maintained by environmental cues and the ability of the monocyte-derived macrophages to undergo homeostatic differentiation into tissue resident macrophages [107]. The disease state is accompanied by monocyte-derived macrophages infiltrating tissues, and progressively losing the ability to support tissue resident macrophages because of the pathologically evolving environmental cues [107]. For instance, SPP1+ macrophage recruitment to the fatty liver from circulating monocytes coincides with the lack of Kupffer cells [50].…”

Section: Discussionmentioning

confidence: 99%

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Systems Level Identification of a Matrisome-Associated Macrophage Polarization State in Multi-Organ Fibrosis

Huang

Mishra

Park

et al. 2022

Preprint

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Tissue fibrosis affects multiple organs and involves a master-regulatory role of macrophages which respond to an initial inflammatory insult common in all forms of fibrosis. The recently unraveled multiorgan heterogeneity of macrophages in healthy and fibrotic human disease suggest that tissue resident macrophages, expressing osteopontin (SPP1), associate with lung and liver fibrosis. However, the conservation of this SPP1+ macrophage population across different tissues, and its specificity to fibrotic diseases with different etiologies remain unclear. Integrating 13 single cell RNA-sequencing datasets to profile 225,985 tissue macrophages from healthy and fibrotic heart, lung, liver, kidney, skin and endometrium, we extended the association of SPP1+ macrophages with fibrosis to all these tissues. We also identified a subpopulation expressing matrisome-associated genes (e.g., matrix metalloproteinases and their tissue inhibitors), functionally enriched for ECM remodeling and cell metabolism, representative of a matrisome-associated macrophage (MAM) polarization state within SPP1+ macrophages. Importantly, the MAM polarization state follows a differentiation trajectory from SPP1+ macrophages, which was conserved across all fibrotic tissues and driven by NFATC1 and HIVEP3 regulons. Unlike SPP1+ macrophages, the MAM polarization state shows a positive association with ageing in mice and humans, and across multiple tissues during homeostasis. These results suggest an advanced, agedependent polarization state of SPP1+ macrophages in fibrotic tissues as a result of prolonged inflammatory cues within each tissue microenvironment.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Systems Level Identification of a Matrisome-Associated Macrophage Polarization State in Multi-Organ Fibrosis

Huang

Mishra

Park

et al. 2022

Preprint

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“…We show that FOLR2 TRMs are embedded in the normal tissue and are spatially segregated from IL4I1, NLRP3, and SPP1, which are tumor-associated. This is an important finding as revealing markers distinguishing TRMs from disease-associated macrophages is a crucial step that enables the study of individual macrophage subset functions and their relevance to disease progression (Park et al 2022). IL4I1, FOLR2, LYVE1, and MARCO label spatially segregated TRM niches in benign colon and breast.…”

Section: Experimental Approachmentioning

confidence: 99%

A spatial map of human macrophage niches reveals context-dependent macrophage functions in colon and breast cancer.

Matusiak¹,

Hickey

Luca

et al. 2023

Preprint

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Tumor-associated macrophages (TAMs) display heterogeneous phenotypes. Yet the exact tissue cues that shape macrophage functional diversity are incompletely understood. Here we discriminate, spatially resolve and reveal the function of five distinct macrophage niches within malignant and benign breast and colon tissue. We found that SPP1 TAMs reside in hypoxic and necrotic tumor regions, and a novel subset of FOLR2 tissue-resident macrophages (TRMs) supports the plasma cell tissue niche. We discover that IL4I1 macrophages populate niches with high cell turnover where they phagocytose dying cells. Significantly, IL4I1 TAMs abundance correlates with anti-PD1 treatment response in breast cancer. Furthermore, NLRP3 inflammasome activation in NLRP3 TAMs correlates with neutrophil infiltration in the tumors and is associated with poor outcome in breast cancer patients. This suggests the NLRP3 inflammasome as a novel cancer immunotherapy target. Our work uncovers context-dependent roles of macrophage subsets and suggests novel predictive markers and macrophage subset-specific therapy targets.

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“…A population of macrophages called microglia are responsible for carrying out this role in the developing brain ( Park et al, 2022 ). However, the mechanism microglia use to efficiently clear dead cells, especially dying neurons, is not fully understood.…”

mentioning

confidence: 99%