The role of airway epithelial cells and innate immune cells in chronic respiratory disease

Holtzman, Michael J.; Byers, Derek E.; Alexander‐Brett, Jennifer; Wang, Xinyu

doi:10.1038/nri3739

Cited by 203 publications

(163 citation statements)

References 175 publications

(141 reference statements)

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“…While many forms of asthma are successfully managed with current treatments with corticosteroids and/or bronchodilators, many asthmatics still suffer from poor management due to steroid resistance or life-threatening exacerbations (1,2). Asthma is commonly viewed as a disease dominated by enhanced adaptive immune responses leading to eosinophilic inflammation, but recent evidence indicates that innate immune responses originating from the respiratory epithelium contribute importantly to enhanced inflammation as well as mucous metaplasia and airway remodeling, which are important hallmarks of allergic asthma (3,4). Moreover, genetic or epigenetic alterations contribute to an altered respiratory epithelium, which is hyperreactive to allergen challenges and thereby mediates exaggerated responses to allergens during exacerbations (3,5).…”

Section: Introductionmentioning

confidence: 99%

DUOX1 mediates persistent epithelial EGFR activation, mucous cell metaplasia, and airway remodeling during allergic asthma

Habibovic¹,

Hristova²,

Heppner³

et al. 2016

JCI Insight

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Section: Introductionmentioning

confidence: 99%

DUOX1 mediates persistent epithelial EGFR activation, mucous cell metaplasia, and airway remodeling during allergic asthma

Habibovic¹,

Hristova²,

Heppner³

et al. 2016

JCI Insight

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“…Other cytokines such as IL‐4, IL‐9, IL‐25, and IL‐33, thymic stromal lymphopoietin, as well as other cytokine‐producing cells such as type 2 innate lymphoid cells, eosinophils, airway epithelial cells, and mast cells (within tissue) also play important roles in mediating HDM‐induced immune response 20, 28, 29, 30.…”

Section: Discussionmentioning

confidence: 99%

Relationship between cytokine expression patterns and clinical outcomes: two population‐based birth cohorts

Prosperi

Simpson

et al. 2015

Clin Experimental Allergy

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SummaryBackgroundModels that incorporate patterns of multiple cytokine responses to allergens, rather than individual cytokine production, may better predict sensitization and asthma.ObjectiveTo characterize the patterns of peripheral blood mononuclear cells’ (PBMCs) cytokine responses to house dust mite (HDM) allergens among children from two population‐based birth cohorts using machine learning techniques.Methods PBMCs collected at 8 years of age from the UK Manchester Asthma and Allergy Study (n = 268) and at 14 years of age from the Australian Raine Study (n = 1374) were cultured with HDM extract (10 μg/ml). Cytokine expression (IL‐13, IL‐5, IFN‐γ, and IL10) was measured in the supernatant. Cytokine patterns were identified using a Gaussian mixture model clustering, and classification stability was assessed by bootstrapping.ResultsA six‐class model indicated complex latent structure of cytokine expression. Based on the characteristics of each class, we designated them as follows: ‘Nonresponders’ (n = 905, 55%); ‘IL‐10 responders’ (n = 49, 3%); ‘IFN‐γ and IL‐13 medium responders’ (n = 56, 3.4%); ‘IL‐13 medium responders’ (n = 351, 21.4%); ‘IL‐5 and IL‐13 medium responders’ (n = 77, 4.7%); and ‘IL‐13 and IL‐5 high responders’ (n = 204, 12.4%). ‘IL‐13 and IL‐5 high responders’ were at much higher risk of HDM sensitization and asthma compared to all other classes, with 88% of children assigned to this class being sensitized and 28.5% having asthma.ConclusionUsing model‐based clustering, we identified several distinct patterns of cytokine response to HDM and observed interplay between cytokine expression level, cytokine patterns (especially IL‐13 and IL‐5), and clinical outcomes. ‘IL‐13 and IL‐5 high responders’ class was strongly associated with HDM sensitization. However, among HDM‐sensitized children, one‐third showed no PBMC response to HDM, and the majority of HDM‐sensitized children did not have asthma or wheeze. Our findings suggest that positive HDM ‘allergy tests’ and asthma are associated with a broad range of immunophenotypes, which may have important implications for the use of cytokine‐targeted treatment approaches.

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“…Cuando se buscaron intencionadamente en tejido post mortem de individuos previamente sanos, las ILC se encontraron cerca de los mastocitos en los pulmones. 45,100 En ratones, las ILC-2 que han tenido contacto previo con un alérgeno responden con una producción más rápida de IL-5 e IL-13 ante un nuevo contacto con el alérgeno, en comparación con los linfocitos Th2.…”

Section: 92unclassified

Las células linfoides innatas y su papel en la regulación de la respuesta inmune

Ruiz‐Sánchez

Cruz‐Zárate

Estrada-Garcı́a

et al. 2017

RAM

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Este artículo debe citarse como: Ruiz-Sánchez BP, Cruz-Zárate D, Estrada-García I, Wong-Baeza I. Las células linfoides innatas y su papel en la regulación de la respuesta inmune. Rev Alerg Mex. 2017;64(3):347-363 AbstractInnate lymphoid cells (ILCs) are lymphocytes lacking antigen recognition receptors and become activated in response to cytokines and through microbe-associated molecular pattern (MAMP) receptors. ILCs are found mainly in mucosal tissues and participate in the immune response against infections and in chronic inflammatory conditions. ILCs are divided in ILC-1, ILC-2 and ILC-3, and these cells have analogue functions to those of immune adaptive response lymphocytes Th1, Th2 and Th17. ILC-1 express T-bet, produce IFNγ, protect against infections with intracellular microorganisms and are related to inflammatory bowel disease immunopathology. ILC-2 express GATA3, produce IL-4, IL-5, IL-13 and amphiregulin, protect against parasitic infections and are related to allergy and obesity immunopathology. ILC-3 express ROR(γt), produce IL-17 and IL-22, protect against fungal infections and contribute to tolerance to intestinal microbiota and intestinal repair. They are related to inflammatory bowel disease and psoriasis immunopathology. In general terms, ILCs maintain homeostasis and coadjuvate in the protection against infections.

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The role of airway epithelial cells and innate immune cells in chronic respiratory disease

Cited by 203 publications

References 175 publications

DUOX1 mediates persistent epithelial EGFR activation, mucous cell metaplasia, and airway remodeling during allergic asthma

DUOX1 mediates persistent epithelial EGFR activation, mucous cell metaplasia, and airway remodeling during allergic asthma

Relationship between cytokine expression patterns and clinical outcomes: two population‐based birth cohorts

Las células linfoides innatas y su papel en la regulación de la respuesta inmune

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