Group 2 innate lymphoid cells are recruited to the nasal mucosa in patients with aspirin-exacerbated respiratory disease

Eastman, Jacqueline J.; Cavagnero, Kellen; DeConde, Adam S.; Kim, Alex S.; Karta, Maya R.; Broide, David H.; Zuraw, Bruce L.; White, Andrew A.; Christiansen, Sandra C.; Doherty, Taylor

doi:10.1016/j.jaci.2016.11.023

Cited by 86 publications

(66 citation statements)

References 39 publications

(64 reference statements)

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“…This is in line with the findings in asthmatic patients where after allergen challenge, D prostanoid receptor 2 (DP2 or CRTH2) positive ILC2s were significantly increased in sputum and correlated with airway eosinophilia . In addition, Eastman et al found that ILC2s were recruited to the nasal mucosa in patients with aspirin‐exacerbated respiratory disease. Using murine models, two recent researches confirmed the important role of ILC2s in exacerbating type 2 inflammation in AR …”

Section: Introductionsupporting

confidence: 84%

Novel innate and adaptive lymphocytes: The new players in the pathogenesis of inflammatory upper airway diseases

Liu

Yao

Wang

et al. 2018

Clin Experimental Allergy

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Host immunity (innate and adaptive immunity) plays essential roles in the pathogenesis of inflammatory upper airway diseases, including allergic rhinitis and chronic rhinosinusitis. Recently, the discovery of novel innate immune cells, particularly innate lymphoid cells, has renewed our view on the role of innate immunity in inflammatory upper airway diseases. Meanwhile, the identification of new subsets of T helper (Th) cells, including Th22, Th9 and follicular Th cells, and regulatory B cells in the adaptive immunity, has broadened our knowledge on the complex immune networks in inflammatory upper airway diseases. In this review, we focus on these newly identified innate and adaptive lymphocytes with their contributions to the immunological disturbance in allergic rhinitis and chronic rhinosinusitis. We further discuss the perspective for future research and potential clinical utility of regulating these novel lymphocytes for the treatment of allergic rhinitis and chronic rhinosinusitis.

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Section: Introductionsupporting

confidence: 84%

Novel innate and adaptive lymphocytes: The new players in the pathogenesis of inflammatory upper airway diseases

Liu

Yao

Wang

et al. 2018

Clin Experimental Allergy

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“…Cysteinyl leukotrienes have long been known to promote airway inflammation, AHR and airway remodeling (1, 2, 38). Recently, we reported increased ILC2s in the nasal mucosa of patients with aspirin exacerbated respiratory disease (AERD) which is characterized by increased CysLTs and PGD2, both of which could recruit and activate ILC2s (39). Further, roles for IL-33 and TSLP in AERD have also been identified, thus supportive of a mediator milieu related to our current studies (40, 41).…”

Section: Discussionmentioning

confidence: 99%

Leukotriene C4 Potentiates IL-33–Induced Group 2 Innate Lymphoid Cell Activation and Lung Inflammation

Lund

Portillo

Cavagnero

et al. 2017

The Journal of Immunology

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Asthma is a complex disease promoted by dysregulated immunity and the presence of many cytokine and lipid mediators. Despite this, there is a paucity of data demonstrating the combined effects of multiple mediators in asthma pathogenesis. Group 2 innate lymphoid cells (ILC2s) have recently been shown to play important roles in the initiation of allergic inflammation, however it is unclear whether lipid mediators such as cysteinyl leukotrienes (CysLTs) that are present in asthma could further amplify the effects of IL-33 on ILC2 activation and lung inflammation. Here we show that airway challenges with the parent CysLT leukotriene C4 (LTC4) given in combination with Iow dose IL-33 to naïve WT mice led to synergistic increases in airway Th2 cytokines, eosinophilia and peribronchial inflammation compared with IL-33 alone. Further, the numbers of proliferating and cytokine-producing lung ILC2s were increased after challenge with both LTC4 and IL-33. Levels of CysLT1R, CysLT2R and candidate LTE4 receptor P2Y12 mRNAs were increased in ILC2s. The synergistic effect of LTC4 with IL-33 was completely dependent upon CysLT1R as CysLT1R−/−, but not CysLT2R−/− mice, had abrogated responses. Further, CysLTs directly potentiated IL-5 and IL-13 production from purified ILC2s stimulated with IL-33 and resulted in NFAT1 nuclear translocation. Finally, CysLT1R−/− mice had reduced lung eosinophils and ILC2 responses after exposure to the fungal allergen Alternaria alternata. Thus, CysLT1R promotes LTC4- and Alternaria-induced ILC2 activation and lung inflammation. These findings suggest that multiple pathways likely exist in asthma to activate ILC2s and propagate inflammatory responses.

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“…Eastman et al . reported that ILC2 cells were specifically recruited to nasal mucosa in patients with aspirin‐exacerbated respiratory disease during aspirin challenge, with a paradoxical increase in urinary PGD 2 metabolite, 11β‐PGF 2 (Eastman et al ., ). This study indicates that PGD 2 may have critical roles in recruiting and activating ILC2s through DP 2 receptors in aspirin‐exacerbated respiratory disease.…”

Section: Pg‐cytokine Crosstalk In Immune and Allergic Inflammationmentioning

confidence: 97%

Prostaglandin‐cytokine crosstalk in chronic inflammation

Yao

Narumiya

2018

British J Pharmacology

191

136

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Chronic inflammation underlies various debilitating disorders including autoimmune, neurodegenerative, vascular and metabolic diseases as well as cancer, where aberrant activation of the innate and acquired immune systems is frequently seen. Since non‐steroidal anti‐inflammatory drugs exert their effects by inhibiting COX and suppressing PG biosynthesis, PGs have been traditionally thought to function mostly as mediators of acute inflammation. However, an inducible COX isoform, COX‐2, is often highly expressed in tissues of the chronic disorders, suggesting an as yet unidentified role of PGs in chronic inflammation. Recent studies have shown that in addition to their short‐lived actions in acute inflammation, PGs crosstalk with cytokines and amplify the cytokine actions on various types of inflammatory cells and drive pathogenic conversion of these cells by critically regulating their gene expression. One mode of such PG‐mediated amplification is to induce the expression of relevant cytokine receptors, which is typically observed in Th1 cell differentiation and Th17 cell expansion, events leading to chronic immune inflammation. Another mode of amplification is cooperation of PGs with cytokines at the transcription level. Typically, PGs and cytokines synergistically activate NF‐κB to induce the expression of inflammation‐related genes, one being COX‐2 itself, which makes PG‐mediated positive feedback loops. This signalling consequently enhances the expression of various NF‐κB‐induced genes including chemokines to macrophages and neutrophils, which enables sustained infiltration of these cells and further amplifies chronic inflammation. In addition, PGs are also involved in tissue remodelling such as fibrosis and angiogenesis. In this article, we review these findings and discuss their relevance to human diseases.

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Group 2 innate lymphoid cells are recruited to the nasal mucosa in patients with aspirin-exacerbated respiratory disease

Cited by 86 publications

References 39 publications

Novel innate and adaptive lymphocytes: The new players in the pathogenesis of inflammatory upper airway diseases

Novel innate and adaptive lymphocytes: The new players in the pathogenesis of inflammatory upper airway diseases

Leukotriene C4 Potentiates IL-33–Induced Group 2 Innate Lymphoid Cell Activation and Lung Inflammation

Prostaglandin‐cytokine crosstalk in chronic inflammation

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