Type 3 ILCs in Lung Disease

Ardain, Amanda; Porterfield, J Zachary; Kløverpris, Henrik N.; Leslie, Alasdair

doi:10.3389/fimmu.2019.00092

Cited by 43 publications

(35 citation statements)

References 111 publications

(117 reference statements)

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“…The recently discovered innate lymphoid cells (ILCs) have broadened our understanding of the pathogenesis of immune diseases including allergy and asthma. ILCs can be divided into 3 groups, ILC1, ILC2, and ILC3, which can also produce cytokines of type1 (such as IFN‐γ and IL‐12), type 2 (IL‐5 and IL‐13), and IL‐17/IL‐22, respectively . The impacts of RhoA on ILCs remain to be elucidated as a future direction of our studies.…”

Section: Discussionmentioning

confidence: 97%

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Ablation of RhoA impairs Th17 cell differentiation and alleviates house dust mite-triggered allergic airway inflammation

Yang

Kalim

et al. 2019

Journal of Leukocyte Biology

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Asthma is a heterogeneous chronic airway inflammation in which Th2 and Th17 cells are key players in its pathogenesis. We have reported that RhoA of Rho GTPases orchestrated glycolysis for Th2 cell differentiation and allergic airway inflammation by the use of a conditional RhoA‐deficient mouse line. However, the role of RhoA in Th17 cells remains to be elucidated. In this study, we investigated the effects of RhoA deficiency on Th17 cells in the context of ex vivo cell culture systems and an in vivo house dust mites (HDM)‐induced allergic airway inflammation. We found that RhoA deficiency inhibited Th17 differentiation and effector cytokine secretion, which was associated with the downregulations of Stat3 and Rorγt, key Th17 transcription factors. Furthermore, loss of RhoA markedly suppressed Th17 and neutrophil‐involved airway inflammation induced by HDM in mice. The infiltrating inflammatory cells in the lungs and bronchoalveolar lavage (BAL) fluids were dramatically reduced in conditional RhoA‐deficient mice. Th17 as well as Th2 effector cytokines were suppressed in the airways at both protein and mRNA levels. Interestingly, Y16, a specific RhoA inhibitor, was able to recapitulate the most phenotypes of RhoA genetic deletion in Th17 differentiation and allergic airway inflammation. Our data demonstrate that RhoA is a key regulator of Th17 cell differentiation and function. RhoA might serve as a potential novel therapeutic target for asthma and other inflammatory disorders.

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Section: Discussionmentioning

confidence: 97%

“…ILCs can be divided into 3 groups, ILC1, ILC2, and ILC3, which can also produce cytokines of type1 (such as IFNand IL-12), type 2 (IL-5 and IL-13), and IL-17/IL-22, respectively. 53,54 The impacts of RhoA on ILCs remain to be elucidated as a future direction of our studies.…”

Section: Discussionmentioning

confidence: 99%

Ablation of RhoA impairs Th17 cell differentiation and alleviates house dust mite-triggered allergic airway inflammation

Yang

Kalim

et al. 2019

Journal of Leukocyte Biology

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“…Further studies are needed to understand the mechanisms of this immune modulation, such as understanding the role of innate lymphoid cells (ILCs) in response to exposure to e-cigarette cartridge components and toxicants. ILC2 and ILC3 are pivotal to the homeostatic response to environmental toxicants with a poised immune response to alleviate lung damage and maintain lung function [49].…”

Section: Resultsmentioning

confidence: 99%

Pulmonary toxicity and inflammatory response of e-cigarettes containing medium-chain triglyceride oil and vitamin E acetate: Implications in the pathogenesis of EVALI but independent of SARS-COV-2 COVID-19 related proteins

Muthumalage

Lucas

Wang

et al. 2020

Preprint

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Recently, there has been an outbreak associated with the use of e-cigarette or vaping products, associated lung injury (EVALI). The primary components of vaping products, vitamin E acetate (VEA) and medium-chain triglycerides (MCT) may be responsible for acute lung toxicity. Currently, little information is available on the physiological and biological effects of exposure to these products. We hypothesized that these e-cig cartridges and their constituents (VEA and MCT) induce pulmonary toxicity, mediated by oxidative damage and inflammatory responses, leading to acute lung injury. We studied the potential mechanisms of cartridge aerosol induced inflammatory response by evaluating the generation of reactive oxygen species by MCT, VEA, and cartridges, and their effects on the inflammatory state of pulmonary epithelium and immune cells both in vitro and in vivo. Cells exposed to these aerosols generated reactive oxygen species, caused cytotoxicity, induced epithelial barrier dysfunction, and elicited an inflammatory response. Using a murine model, the parameters of acute toxicity to aerosol inhalation were assessed. Infiltration of neutrophils and lymphocytes was accompanied by significant increases in IL-6, eotaxin, and G-CSF in the bronchoalveolar lavage fluid (BALF). In mouse plasma, eicosanoid inflammatory mediators, leukotrienes, were significantly increased. Plasma from e-cig users also showed increased levels of hydroxyeicosatetraenoic acid (HETEs) and various eicosanoids. Exposure to e-cig cartridge aerosols showed the most significant effects and toxicity compared to MCT and VEA. In addition, we determined at SARS-COV-2 related proteins and found no impact associated with aerosol exposures from these tested cartridges. Overall, this study demonstrates acute exposure to specific e-cig cartridges induces in vitro cytotoxicity, barrier dysfunction, and inflammation and in vivo mouse exposure induces acute inflammation with elevated pro-inflammatory markers in the pathogenesis of EVALI.

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“…99,100 Interestingly, the majority of studies to date focus on ILC2, however, ILC3 are in fact the most prevalent group in the human lung and their rapid secretion of IL-17A and IL-22 has led to their investigation in inflammatory and infectious diseases. 101 Interestingly, although the importance of ILC3 as a source of granulocytemacrophage colony-stimulating factor, an important cytokine in pulmonary host defence, in the lung is unknown, ILC3 in the gut are known to orchestrate inflammation.…”

Section: Innate Lymphoid Cellsmentioning

confidence: 99%

Spatiotemporal Cellular Networks Maintain Immune Homeostasis in the Lung

Borger¹

2020

EMJ Respir

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A dynamic and intricately connected tissue-resident immune cell network continuously monitors the lungs, which are incessantly subjected to external environmental insults. The lungs are protected by the respiratory epithelium, which not only serves as a physical barrier through mucociliary mechanisms, but also a reactive one that can release cytokines, chemokines, and other defence proteins in response to danger signals. In the maintenance of pulmonary homeostasis in health, the lung-resident immune cell network instructs tolerance to innocuous particulates and can rapidly and efficiently drive immunity and memory to pathogenic antigens. This review examines the spatiotemporal dynamics that underlie the exquisite network of highly specialised immune cells and their mediators in the support of pulmonary tissue homeostasis and effective lung immunity in health. In particular, this review examines the specialised immune cells that reside in distinct populations within the diverse compartments of the lung, and the molecular signals that retain and recruit lung-resident immune cells, to further our understanding of how these can be targeted therapeutically to return inflamed or diseased lungs to homeostasis.

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Type 3 ILCs in Lung Disease

Cited by 43 publications

References 111 publications

Ablation of RhoA impairs Th17 cell differentiation and alleviates house dust mite-triggered allergic airway inflammation

Ablation of RhoA impairs Th17 cell differentiation and alleviates house dust mite-triggered allergic airway inflammation

Pulmonary toxicity and inflammatory response of e-cigarettes containing medium-chain triglyceride oil and vitamin E acetate: Implications in the pathogenesis of EVALI but independent of SARS-COV-2 COVID-19 related proteins

Spatiotemporal Cellular Networks Maintain Immune Homeostasis in the Lung

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