Macrophage and Innate Lymphoid Cell Interplay in the Genesis of Fibrosis

Hams, Emily; Bermingham, Rachel; Fallon, Padraic G.

doi:10.3389/fimmu.2015.00597

Cited by 55 publications

(53 citation statements)

References 120 publications

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“…Airway macrophages secrete numerous profibrotic soluble mediators, chemokines and matrix metalloproteases, and are ideally placed to regulate lung fibrosis as they are located in close proximity to epithelial cells and subepithelial myofibroblasts, cells with the capacity to generate large amounts of collagen . The triad of epithelial‐derived innate cytokines, IL‐33, IL‐25 and thymic stromal lymphopoietin drive macrophage polarization during tissue damage promoting an anti‐inflammatory and pro‐tissue repair/heal phenotype in IPF . Fibrosis is induced by both tissue‐resident and recruited macrophages.…”

Section: Idiopathic Pulmonary Fibrosismentioning

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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Section: Idiopathic Pulmonary Fibrosismentioning

confidence: 99%

Airway macrophages as the guardians of tissue repair in the lung

2019

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“…However, while mechanistic and functional contributions of ILC in animal models of asthma and COPD have been studied to a certain extent, there is very limited evidence for a potential role in human disease conditions so far. With regards to lung fibrosis, the potential role of ILC is discussed in a comprehensive review [95]. In brief, given that IL-17A plays a key role in pulmonary inflammation and fibrosis in COPD, IPF, and CF [96–98], and given that ILC3 are an essential source of IL-17 at mucosal sites ILC3s are suggested to function as early orchestrators of lung tissue remodeling and fibrogenesis.…”

Section: Innate Lymphoid Cellsmentioning

confidence: 99%

Innate Immunity of the Lung: From Basic Mechanisms to Translational Medicine

et al. 2018

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The respiratory tract is faced daily with 10,000 L of inhaled air. While the majority of air contains harmless environmental components, the pulmonary immune system also has to cope with harmful microbial or sterile threats and react rapidly to protect the host at this intimate barrier zone. The airways are endowed with a broad armamentarium of cellular and humoral host defense mechanisms, most of which belong to the innate arm of the immune system. The complex interplay between resident and infiltrating immune cells and secreted innate immune proteins shapes the outcome of host-pathogen, host-allergen, and host-particle interactions within the mucosal airway compartment. Here, we summarize and discuss recent findings on pulmonary innate immunity and highlight key pathways relevant for biomarker and therapeutic targeting strategies for acute and chronic diseases of the respiratory tract.

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“…Given that ETS in this study appeared to shift the immune response from Th1 towards Th2 type disease, and that tissue fibrosis is associated with Th2 type inflammation (Barron and Wynn, 2011), it makes sense that greater levels of tissue fibrosis would be observed in ETS-exposed mice. The shift towards Th2 type immune response may be due to alternate activation of the ILC2s which has also been shown to increase risk for tissue fibrosis (Hams et al, 2015). Additional factors, such as altered macrophage activation state and fiber clearance could also be affecting the degree of tissue fibrosis in the mice.…”

Section: Discussionmentioning

confidence: 99%

Early life exposure to environmental tobacco smoke alters immune response to asbestos via a shift in inflammatory phenotype resulting in increased disease development

Brown

Holian

Pinkerton

et al. 2016

Inhalation Toxicology

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Asbestos in combination with tobacco smoke exposure reportedly leads to more severe physiological consequences than asbestos alone; limited data also show an increased disease risk due to environmental tobacco smoke (ETS) exposure. Environmental influences during gestation and early lung development can result in physiological changes that alter risk for disease development throughout an individual’s lifetime. Therefore, maternal lifestyle may impact the ability of offspring to subsequently respond to environmental insults and alter overall disease susceptibility. In this study, we examined the effects of exposure to ETS in utero and during early postnatal development on asbestos-related inflammation and disease in adulthood. ETS exposure in utero appeared to shift inflammation towards a Th2 phenotype, via suppression of Th1 inflammatory cytokine production. This effect was further pronounced in mice exposed to ETS in utero and during early postnatal development. In utero ETS exposure led to increased collagen deposition, a marker of fibrotic disease, when the offspring was later exposed to asbestos, which was further increased with additional ETS exposure during early postnatal development. These data suggest that ETS exposure in utero alters the immune responses and leads to greater disease development after asbestos exposure, which is further exacerbated when exposure to ETS continues during early postnatal development.

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Macrophage and Innate Lymphoid Cell Interplay in the Genesis of Fibrosis

Cited by 55 publications

References 120 publications

Airway macrophages as the guardians of tissue repair in the lung

Airway macrophages as the guardians of tissue repair in the lung

Innate Immunity of the Lung: From Basic Mechanisms to Translational Medicine

Early life exposure to environmental tobacco smoke alters immune response to asbestos via a shift in inflammatory phenotype resulting in increased disease development

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