Hyaluronan Receptor LYVE-1-Expressing Macrophages Maintain Arterial Tone through Hyaluronan-Mediated Regulation of Smooth Muscle Cell Collagen

Lim, Hwee Ying; Lim, Sheau Yng; Tan, Chee Leong; Thiam, Chung Hwee; Goh, Chi Ching; Carbajo, Daniel; Chew, Samantha Hui Shang; See, Peter; Chakarov, Svetoslav; Wang, Xiao Nong; Lim, Lynette; Johnson, Louise A.; Lum, Josephine; Fong, Chui Yee; Bongso, Ariff; Biswas, Arijit; Goh, Chern; Evrard, Maximilien; Yeo, Kim Pin; Basu, Ranu; Wang, Jun Kit; Tan, Yingrou; Jain, Rohit; Tikoo, Shweta; Choong, Cleo; Weninger, Wolfgang; Poidinger, Michael; Stanley, Richard; Collin, Matthew; Tan, Nguan Soon; Ng, Lai Guan; Jackson, David G.; Ginhoux, Florent; Angeli, Véronique

doi:10.1016/j.immuni.2018.06.008

Cited by 251 publications

(166 citation statements)

References 49 publications

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“…4b) – forming two distinct PA macrophage sub-clusters. LYVE1 and SCN9A define one subset of arterial resident macrophages known to modulate arterial tone through smooth muscle collagen degradation 15,16 . The absence of these cells in the AC indicates dysfunctional arterial homeostasis in this region.…”

Section: Resultsmentioning

confidence: 99%

Decoding the transcriptome of atherosclerotic plaque at single-cell resolution

Alsaigh¹,

Evans²,

Frankel

et al. 2020

Preprint

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Atherogenesis involves an interplay of inflammation, tissue remodeling and cellular transdifferentiation (CTD), making it especially difficult to precisely delineate its pathophysiology. Here we examine the single-cell transcriptome of entire atherosclerotic core (AC) plaques and patient-matched proximal adjacent (PA) portions of carotid artery tissue from patients undergoing carotid endarterectomy. We use a novel tissue dissociation strategy, single-cell RNA sequencing, and systems-biology approaches to analyze the transcriptional profiles of six main cell populations and identify key gene drivers of pathogenic biological processes in vascular smooth muscle cells (VSMCs) and endothelial cells (ECs). Our results reveal an anatomic continuum whereby PA cells promote and respond to inflammatory processes and eventually transition through CTD into matrix-secreting cells in the AC. Inflammatory signaling in PA ECs is driven by IL6, while TNFa signaling defines inflammation in both PA ECs and VSMCs. Furthermore, we identify POSTN, SPP1 and IBSP in AC VSMCs, and ITLN1, SCX and S100A4 in AC ECs as key drivers of CTD in the atherosclerotic core. These results establish an anatomic framework for atherogenesis and suggest a site-specific strategy for disruption of disease progression.

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Section: Resultsmentioning

confidence: 99%

Decoding the transcriptome of atherosclerotic plaque at single-cell resolution

Alsaigh¹,

Evans²,

Frankel

et al. 2020

Preprint

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“…EMP-derived macrophages are characterized by high expression of Lyve-1 , Stab1, Gas6 , and Cd163 , among other genes. The hyaluronan receptor LYVE-1 has been identified as a key marker of resident macrophages in cardiovascular tissues 19 , 45 . In arteries, LYVE-1 exerts important homeostatic functions by controlling collagen expression in vascular smooth muscle cells 19 .…”

Section: Discussionmentioning

confidence: 99%

“…The hyaluronan receptor LYVE-1 has been identified as a key marker of resident macrophages in cardiovascular tissues 19 , 45 . In arteries, LYVE-1 exerts important homeostatic functions by controlling collagen expression in vascular smooth muscle cells 19 . Further, LYVE-1 provides pro-angiogenic functions 18 .…”

Section: Discussionmentioning

confidence: 99%

Ontogeny of arterial macrophages defines their functions in homeostasis and inflammation

et al. 2020

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Arterial macrophages have different developmental origins, but the association of macrophage ontogeny with their phenotypes and functions in adulthood is still unclear. Here, we combine macrophage fate-mapping analysis with single-cell RNA sequencing to establish their cellular identity during homeostasis, and in response to angiotensin-II (AngII)-induced arterial inflammation. Yolk sac erythro-myeloid progenitors (EMP) contribute substantially to adventitial macrophages and give rise to a defined cluster of resident immune cells with homeostatic functions that is stable in adult mice, but declines in numbers during ageing and is not replenished by bone marrow (BM)-derived macrophages. In response to AngII inflammation, increase in adventitial macrophages is driven by recruitment of BM monocytes, while EMP-derived macrophages proliferate locally and provide a distinct transcriptional response that is linked to tissue regeneration. Our findings thus contribute to the understanding of macrophage heterogeneity, and associate macrophage ontogeny with distinct functions in health and disease.

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“…Thus, if tissue-resident macrophages contribute to FAP clearance, as has been reported for inflammatory, monocyte-derived macrophages (Lemos et al, 2015) some of the effects of aging or Mertk loss in macrophages might be attributed to the persistence of these cells. Finally, while the expression of Cx3cr1 in the skeletal muscle is limited to macrophages, Cx3cr1 is also expressed on monocytes and LYVE1-expressing macrophages associated with the vasculature and nerve fibers (Lim et al, 2018;Schaum et al, 2018). We therefore cannot completely exclude off target effects related to global deletion of Cx3cr1 in our system.…”

Section: Discussionmentioning

confidence: 99%

Impaired phagocytic function in CX3CR1⁺ tissue-resident skeletal muscle macrophages prevents muscle recovery after influenza A virus-induced pneumonia in aged mice

Runyan¹,

Welch²,

Lecuona³

et al. 2019

Preprint

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Skeletal muscle dysfunction in survivors of pneumonia is a major cause of lasting morbidity that disproportionately affects older individuals. We found that skeletal muscle recovery was impaired in aged compared with young mice after influenza A virus-induced pneumonia. In young mice, recovery of muscle loss was associated with expansion of tissue-resident skeletal muscle macrophages and downregulation of MHC II expression, followed by a proliferation of muscle satellite cells. These findings were absent in aged mice and in mice deficient in Cx3cr1. Transcriptomic profiling of tissue-resident skeletal muscle macrophages from aged compared with young mice showed downregulation of pathways associated with phagocytosis and proteostasis, and persistent upregulation of inflammatory pathways. Consistently, skeletal muscle macrophages from aged mice failed to downregulate MHCII expression during recovery from influenza A virus induced pneumonia and showed impaired phagocytic function in vitro. Like aged animals, mice deficient in the phagocytic receptor Mertk showed no macrophage expansion, MHCII downregulation or satellite cell proliferation and failed to recover skeletal muscle function after influenza A pneumonia. Our data suggest that a loss of phagocytic function in a CX3CR1 + tissue-resident skeletal muscle macrophage population in aged mice precludes satellite cell proliferation and recovery of skeletal muscle function after influenza A pneumonia.

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Hyaluronan Receptor LYVE-1-Expressing Macrophages Maintain Arterial Tone through Hyaluronan-Mediated Regulation of Smooth Muscle Cell Collagen

Cited by 251 publications

References 49 publications

Decoding the transcriptome of atherosclerotic plaque at single-cell resolution

Decoding the transcriptome of atherosclerotic plaque at single-cell resolution

Ontogeny of arterial macrophages defines their functions in homeostasis and inflammation

Impaired phagocytic function in CX3CR1⁺ tissue-resident skeletal muscle macrophages prevents muscle recovery after influenza A virus-induced pneumonia in aged mice

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Hyaluronan Receptor LYVE-1-Expressing Macrophages Maintain Arterial Tone through Hyaluronan-Mediated Regulation of Smooth Muscle Cell Collagen

Cited by 251 publications

References 49 publications

Decoding the transcriptome of atherosclerotic plaque at single-cell resolution

Decoding the transcriptome of atherosclerotic plaque at single-cell resolution

Ontogeny of arterial macrophages defines their functions in homeostasis and inflammation

Impaired phagocytic function in CX3CR1+ tissue-resident skeletal muscle macrophages prevents muscle recovery after influenza A virus-induced pneumonia in aged mice

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Product

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Impaired phagocytic function in CX3CR1⁺ tissue-resident skeletal muscle macrophages prevents muscle recovery after influenza A virus-induced pneumonia in aged mice