Pulmonary group 2 innate lymphoid cells: surprises and challenges

Starkey, Malcolm R.; McKenzie, Andrew N. J.; Belz, Gabrielle T.; Hansbro, Philip M.

doi:10.1038/s41385-018-0130-4

Cited by 63 publications

(70 citation statements)

References 206 publications

(289 reference statements)

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“…Numerous studies suggest that mepolizumab (anti-IL-5 monoclonal antibody) treatment reduces the requirement for oral steroids in severe eosinophilic asthma [96,97]. Furthermore, there are known links between innate type 2 inducers and mediators IL-33, IL-25 and TSLP (thymic stromal lymphopoietin), and type 2 innate lymphoid and T-helper cells and steroid resistance [98][99][100]. Antibodies against these factors may prove to be somewhat effective in severe disease [4,99,101].…”

Section: Biologicsmentioning

confidence: 99%

Cellular mechanisms underlying steroid-resistant asthma

et al. 2019

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Severe steroid-resistant asthma is clinically important, as patients with this form of the disease do not respond to mainstay corticosteroid therapies. The heterogeneity of this form of asthma and poor understanding of the pathological mechanisms involved hinder the identification of therapeutic targets and the development of more effective therapies. A major limiting factor in the understanding of severe steroid-resistant asthma is the existence of multiple endotypes represented by different immunological and inflammatory phenotypes, particularly in adults. Several clinical and experimental studies have revealed associations between specific respiratory infections and steroid-resistant asthma in adults. Here, we discuss recent findings from other authors as well as our own studies that have developed novel experimental models for interrogating the association between respiratory infections and severe steroid-resistant asthma. These models have enabled the identification of new therapies using macrolides, as well as several novel disease mechanisms, including the microRNA-21/phosphoinositide 3-kinase/histone deacetylase 2 axis and NLRP3 inflammasomes, and highlight the potential of these mechanisms as therapeutic targets.

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Section: Biologicsmentioning

confidence: 99%

Cellular mechanisms underlying steroid-resistant asthma

et al. 2019

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“…These studies demonstrated that the protective effects of IL‐33 were significantly diminished in the absence of ILC2s . However, these mice were also depleted of other CD90 expressing cells including T reg cells, which may also be critical for this renoprotection . Furthermore, a complex bidirectional relationship exists between ILC2s and T reg .…”

Section: Ilc2s As a Potential Cellular Therapy In Renal Injurymentioning

confidence: 97%

“…However, these mice were also depleted of other CD90 expressing cells including T reg cells, which may also be critical for this renoprotection . Furthermore, a complex bidirectional relationship exists between ILC2s and T reg . This concept is supported by studies examining the IL233 hybrid cytokine .…”

Section: Ilc2s As a Potential Cellular Therapy In Renal Injurymentioning

confidence: 98%

Emerging therapeutic potential of group 2 innate lymphoid cells in acute kidney injury

Cameron

Jiang

Loering

et al. 2019

The Journal of Pathology

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Acute kidney injury (AKI) remains a global challenge and, despite the availability of dialysis and transplantation, can be fatal. Those that survive an AKI are at increased risk of developing chronic kidney disease and end stage renal failure. Understanding the fundamental mechanisms underpinning the pathophysiology of AKI is critical for developing novel strategies for diagnosis and treatment. A growing body of evidence indicates that amplifying type 2 immunity may have therapeutic potential in kidney injury and disease. Of particular interest are the recently described subset of innate immune cells, termed group 2 innate lymphoid cells (ILCs). Group 2 ILCs are crucial tissue‐resident immune cells that maintain homeostasis and regulate tissue repair at multiple organ sites, including the kidney. They are critical mediators of type 2 immune responses following infection and injury. The existing literature suggests that activation of group 2 ILCs and production of a local type 2 immune milieu is protective against renal injury and associated pathology. In this review, we describe the emerging role for group 2 ILCs in renal homeostasis and repair. We provide an in‐depth discussion of the most recent literature that use preclinical models of AKI and assess the therapeutic effect of modulating group 2 ILC function. We debate the potential for targeting these cells as novel cellular therapies in AKI and discuss the implications for future studies and translation. Copyright © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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“…ILC2 initiates and maintains the adaptive Th2 immune response which can be activated by IL-25, IL-33 and TSLP. 40 To determine how ITGB4…”

Section: Increased Expression Of Tslp In Itgb4deficient Airway Epitmentioning

confidence: 99%

Airway epithelial ITGB4 deficiency in early life mediates pulmonary spontaneous inflammation and enhanced allergic immune response

Tang

Lin

et al. 2020

J Cellular Molecular Medi

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Lung immune responses to respiratory pathogens and allergens are initiated in early life which will further influence the later onset of asthma. The airway epithelia form the first mechanical physical barrier to allergic stimuli and environmental pollutants, which is also the key regulator in the initiation and development of lung immune response. However, the epithelial regulation mechanisms of early‐life lung immune responses are far from clear. Our previous study found that integrin β4 (ITGB4) is decreased in the airway epithelium of asthma patients with specific variant site. ITGB4 deficiency in adult mice aggravated the lung Th2 immune responses and enhanced airway hyper‐responsiveness (AHR) with a house dust mite (HDM)‐induced asthma model. However, the contribution of ITGB4 to the postnatal lung immune response is still obscure. Here, we further demonstrated that ITGB4 deficiency following birth mediates spontaneous lung inflammation with ILC2 activation and increased infiltration of eosinophils and lymphocytes. Moreover, ITGB4 deficiency regulated thymic stromal lymphopoietin (TSLP) production in airway epithelial cells through EGFR pathways. Neutralization of TSLP inhibited the spontaneous inflammation significantly in ITGB4‐deficient mice. Furthermore, we also found that ITGB4 deficiency led to exaggerated lung allergic inflammation response to HDM stress. In all, these findings indicate that ITGB4 deficiency in early life causes spontaneous lung inflammation and induces exaggerated lung inflammation response to HDM aeroallergen.

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Pulmonary group 2 innate lymphoid cells: surprises and challenges

Cited by 63 publications

References 206 publications

Cellular mechanisms underlying steroid-resistant asthma

Cellular mechanisms underlying steroid-resistant asthma

Emerging therapeutic potential of group 2 innate lymphoid cells in acute kidney injury

Airway epithelial ITGB4 deficiency in early life mediates pulmonary spontaneous inflammation and enhanced allergic immune response

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