Group 2 innate lymphoid cells promote airway hyperresponsiveness through production of VEGFA

Shen, Xiaofei; Pasha, M. Asghar; Hidde, Kelsi; Khan, Adil I.; Liang, Man; Guan, Wenxian; Ding, Yi-Tao; Haczku, Angela Franciska; Yang, Qi

doi:10.1016/j.jaci.2018.01.005

Cited by 25 publications

(37 citation statements)

References 13 publications

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“…25 FlexiVent system (SCIREQ) was used to measure airway hyperresponsiveness as we previously described. 8 Mouse protocols were approved by the Institutional Animal Care and Use Committee of Albany Medical College.…”

Section: Mice Allergen and Cytokine Challenge Adoptive Transfer mentioning

confidence: 99%

“…[3][4][5][6] Recent studies from us and others have indicated the importance of group-2 innate lymphoid cells (ILC2), a unique subset of innate effector cells, in asthma pathogenesis. 3,5,[7][8][9] ILC2 are a distinct subset of non-circulating tissue-resident cells that are enriched at mucosal barrier sites including the gut and the lung. 10 Upon activation, ILC2 are potent producers of type-2 cytokines IL-5 and IL-13 as well as other critical effector molecules such as VEGFA.…”

Section: Introductionmentioning

confidence: 99%

“…10 Upon activation, ILC2 are potent producers of type-2 cytokines IL-5 and IL-13 as well as other critical effector molecules such as VEGFA. 2,8 Studies with mouse models suggested that activated ILC2 can induce eosinophil infiltration, promote neutrophilic inflammation and mediate airway hyperresponsiveness (AHR). 8,11 ILC2 may also promote pathogenic helper 2 T cell responses (Th2) by providing co-stimulatory molecules and presenting antigens.…”

Section: Introductionmentioning

confidence: 99%

“…2,8 Studies with mouse models suggested that activated ILC2 can induce eosinophil infiltration, promote neutrophilic inflammation and mediate airway hyperresponsiveness (AHR). 8,11 ILC2 may also promote pathogenic helper 2 T cell responses (Th2) by providing co-stimulatory molecules and presenting antigens. 12,13 ILC2 in asthma patients exhibited an activated phenotype, demonstrated by increased cellularity, and enhanced expression of IL-5, IL-13 and VEGFA.…”

Section: Introductionmentioning

confidence: 99%

“…12,13 ILC2 in asthma patients exhibited an activated phenotype, demonstrated by increased cellularity, and enhanced expression of IL-5, IL-13 and VEGFA. 8,14 However, the molecular mechanisms that drive ILC2 activation in asthma are not well understood.…”

Section: Introductionmentioning

confidence: 99%

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A critical role for c‐Myc in group 2 innate lymphoid cell activation

Pan

Liang

et al. 2020

Allergy

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Background: Asthma is a complicated chronic inflammatory disorder characterized by airway inflammation and bronchial hyperresponsiveness. Group 2 innate lymphoid cells (ILC2) are tissue-resident innate effector cells that can mediate airway inflammation and hyperresponsiveness through production of IL-5, IL-13 and VEGFA. ILC2 in asthma patients exhibit an activated phenotype. However, molecular pathways that control ILC2 activation are not well understood.Methods: MYC expression was examined in ILC2 sorted from peripheral blood of healthy controls and asthma patients or cultured with or without activating cytokines. CRISPR knockout technique was used to delete c-Myc in primary murine lung ILC2 or an ILC2 cell line. Cell proliferation was examined, gene expression pattern was profiled by genome-wide microarray analysis, and direct gene targets were identified by Chromatin immunoprecipitation (ChIP). ILC2 responses, airway inflammation and airway hyperresponsiveness were examined in Balb/c mice challenged with Alternaria extracts, with or without treatment with JQ1. Results: ILC2 from asthma patients expressed increased amounts of MYC. Deletion of c-Myc in ILC2 results in reduced proliferation, decreased cytokine production, and reduced expression of many lymphocyte activation genes. ChIP identified Stat6 as a direct gene target of c-Myc in ILC2. In vivo inhibition of c-Myc by JQ1 treatment repressed ILC2 activity and suppressed Alternaria-induced airway inflammation and AHR. Conclusion: c-Myc expression is upregulated during ILC2 activation. c-Myc is essential for ILC2 activation and their in vivo pathogenic effects. These findings suggest that targeting c-Myc may unlock novel strategies to combat asthma or asthma exacerbation. K E Y W O R D S airway hyperresponsiveness, asthma, c-Myc, ILC2 S U PP O RTI N G I N FO R M ATI O N Additional supporting information may be found online in the Supporting Information section. How to cite this article: Ye L, Pan J, Liang M, et al. A critical role for c-Myc in group 2 innate lymphoid cell activation. Allergy. 2020;75:841-852. https ://doi.

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Section: Mice Allergen and Cytokine Challenge Adoptive Transfer mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A critical role for c‐Myc in group 2 innate lymphoid cell activation

Pan

Liang

et al. 2020

Allergy

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Lung development and emerging roles for type 2 immunity

Loering

Cameron

Starkey

et al. 2019

The Journal of Pathology

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Lung development is a complex process mediated through the interaction of multiple cell types, factors and mediators. In mice, it starts as early as embryonic day 9 and continues into early adulthood. The process can be separated into five different developmental stages: embryonic, pseudoglandular, canalicular, saccular, and alveolar. Whilst lung bud formation and branching morphogenesis have been studied extensively, the mechanisms of alveolarisation are incompletely understood. Aberrant lung development can lead to deleterious consequences for respiratory health such as bronchopulmonary dysplasia (BPD), a disease primarily affecting preterm neonates, which is characterised by increased pulmonary inflammation and disturbed alveolarisation. While the deleterious effects of type 1-mediated inflammatory responses on lung development have been well established, the role of type 2 responses in postnatal lung development remains poorly understood. Recent studies indicate that type 2-associated immune cells, such as group 2 innate lymphoid cells and alveolar macrophages, are increased in number during postnatal alveolarisation. Here, we present the current state of understanding of the postnatal stages of lung development and the key cell types and mediators known to be involved. We also provide an overview of how stem cells are involved in lung development and regeneration, and the negative influences of respiratory infections.No conflicts of interest were declared. Recently, it has been shown that in mice, mechanical forces are involved in organ development by controlling the ratio of fixed and rotating spindles needed for normal

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Innate Lymphoid Cells in Airway Inflammation

Pasha

Yang

2021

Advances in Experimental Medicine and Biology

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Group 2 innate lymphoid cells promote airway hyperresponsiveness through production of VEGFA

Cited by 25 publications

References 13 publications

A critical role for c‐Myc in group 2 innate lymphoid cell activation

A critical role for c‐Myc in group 2 innate lymphoid cell activation

Lung development and emerging roles for type 2 immunity

Innate Lymphoid Cells in Airway Inflammation

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