Local amplifiers of IL-4Rα–mediated macrophage activation promote repair in lung and liver

Minutti, Carlos M.; Jackson-Jones, Lucy H.; García-Fojeda, Belén; Knipper, Johanna A.; Sutherland, Tara E.; Logan, Nicola; Ringqvist, Emma; Guillamat-Prats, Raquel; Ferenbach, David A.; Artigas, Antonio; Stamme, Cordula; Chroneos, Zissis C.; Zaiss, Dietmar M.; Casals, Cristina; Allen, Judith E.

doi:10.1126/science.aaj2067

Cited by 175 publications

(182 citation statements)

References 47 publications

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“…These M2‐differentiated THP‐1 cells also increased dermal fibroblast expression of α‐SMA, a feature of myofibroblasts, indicating that fibroblasts were differentiated into myofibroblasts . Furthermore, abrogation of IL‐4Rα signaling in macrophages impaired wound repair in in vivo models of wound healing by skin punch biopsy, chemical‐induced injury or invasive helminth infection‐induced injury . Mechanistically, M2 macrophages initiate wound repair through numerous pathways including growth factors and matrix metalloproteinases, summarized in Figure and in recent reviews .…”

Section: Wound‐healing Macrophage Activation and Functionmentioning

confidence: 94%

“…IL‐4Rα signaling also stimulates tissue‐resident macrophage proliferation, which can have the beneficial outcome of expanding and activating the effector macrophage population for wound healing . Here, additional signals from the tissue environment promoted the IL‐4‐induced wound‐healing capacity of M2 macrophages.…”

Section: Wound‐healing Macrophage Activation and Functionmentioning

confidence: 99%

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Macrophages in wound healing: activation and plasticity

2019

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Macrophages are critically involved in wound healing, from dampening inflammation to clearing cell debris and coordinating tissue repair. Within the wound, the complexity of macrophage function is increasingly recognized, with adverse outcomes when macrophages are inappropriately activated, such as in fibrosis or chronic non‐healing wounds. Recent advances in in vivo and translational wound models, macrophage‐specific deletions and new technologies to distinguish macrophage subsets, have uncovered the vast spectrum of macrophage activation and effector functions. Here, we summarize the main players in wound‐healing macrophage activation and function, including cytokines, apoptotic cells, nucleotides and mechanical stimuli. We highlight recent studies demonstrating cooperation between these factors for optimal wound healing. Next, we describe recent technologies such as cell tracking and single‐cell RNA‐seq, which have uncovered remarkable plasticity and heterogeneity in blood‐derived or tissue‐resident macrophages and discuss the implications for wound healing. Lastly, we evaluate macrophage dysfunction in aberrant wound healing that occurs in aging, diabetes and fibrosis. A better understanding of the longevity and plasticity of wound‐healing macrophages, and identification of unique macrophage subsets or specific effector molecules in wound healing, would shed light on the therapeutic potential of manipulating macrophage function for optimal wound healing.

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Section: Wound‐healing Macrophage Activation and Functionmentioning

confidence: 94%

Section: Wound‐healing Macrophage Activation and Functionmentioning

confidence: 99%

Macrophages in wound healing: activation and plasticity

2019

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“…In a helminth Th2 inflammation model, IL‐4 receptor signaling on AM enhanced the expression of insulin‐like growth factor 1 and IL‐10 and stimulated the development of prohealing macrophages, which were critical for timely resolution of tissue damage . Furthermore, following worm infection or fibrosis, surfactant protein A in the lung enhanced IL‐4‐mediated proliferation and activation of AM and expression of the receptor Myo18A …”

Section: Macrophages In Pulmonary Tissue Repairmentioning

confidence: 99%

Airway macrophages as the guardians of tissue repair in the lung

2019

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The lungs present a challenging immunological dilemma for the host. Anatomically positioned at the environmental interface, they are constantly exposed to antigens, pollutants and microbes, while simultaneously facilitating vital gas exchange. Remarkably, the lungs maintain a functionally healthy state, ignoring harmless inhaled proteins, adapting to toxic environmental insults and limiting immune responses to allergens and pathogenic microbes. This functional strategy of environmental adaptation maintains immune defense, reduces tissue damage, and promotes and sustains lung immune tolerance. At steady state, airway macrophages produce low levels of cytokines, and suppress the induction of innate and adaptive immunity. These cells are primary initiators of lung innate immunity and possess high phagocytic activity to clear particulate antigens and apoptotic cell debris from the airways to regulate the response to infection and inflammation. In response to epithelial injury, resident and recruited macrophages drive tissue repair. In this review, we will focus on the functional importance of macrophages in tissue homeostasis and inflammation in the lung and highlight how environmental cues alter the plasticity and function of lung airway macrophages. We will also discuss mechanisms employed by pulmonary macrophages to promote resolution of tissue inflammation, and how and when this balance is perturbed, they contribute to pathological remodeling in acute and chronic infections and diseases such as asthma, idiopathic pulmonary fibrosis and chronic obstructive pulmonary disease.

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“…Arg‐1 expression by macrophages is required for both helminth killing and the repair of tissue damage caused by these large multicellular pathogens . C1q, a component of the complement pathway, has also been shown to contribute to the activation of M(IL‐4) and has been shown to be important not only for the tissue repair following helminth infection, but also following Listeria infection . Lastly, in the context of a sterile injury of the central nervous system, microglia with a M(IL‐4) phenotype have been described to produce Activin‐A which promotes oligodendrocyte differentiation and remyelination .…”

Section: Macrophages As Multifunctional Players In Tissue Repairmentioning

confidence: 99%

Neutrophil–macrophage cooperation and its impact on tissue repair

Bouchery

Harris

2019

Immunol Cell Biol

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Immune cells are rapidly recruited to a site of injury or infection. Although the importance of phagocytic immune cells in clearing bacteria has long been appreciated, the advent of technologies allowing more in‐depth analysis of cellular function, such as intravital microscopy and the use of genetically modified animal models, has allowed much deeper insight into the complex roles of these cells play during tissue repair. Many immune cells contribute to the repair process; however, this review will concentrate on the involvement of the phagocytes, namely macrophages and neutrophils, with a particular focus on our more recent understanding of how interactions between these two cell types impact on the final outcome of tissue repair.

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Local amplifiers of IL-4Rα–mediated macrophage activation promote repair in lung and liver

Cited by 175 publications

References 47 publications

Macrophages in wound healing: activation and plasticity

Macrophages in wound healing: activation and plasticity

Airway macrophages as the guardians of tissue repair in the lung

Neutrophil–macrophage cooperation and its impact on tissue repair

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