Barrier function of the nasal mucosa in health and type‐2 biased airway diseases

Zhang, N.; Crombruggen, Koen Van; Gevaert, Elien; Bachert, Claus

doi:10.1111/all.12809

Cited by 109 publications

(97 citation statements)

References 110 publications

(147 reference statements)

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“…Soyka et al (45) reported reduced barrier function in tissues from CRS patients. Many studies have confirmed the loss of epithelial markers and gain of mesenchymal markers in CRS (reviewed in 46). Markers shown in Figure 2 in blue are epithelial markers that are lost in CRS, and those shown in red are mesenchymal markers that are gained in CRS.…”

Section: Tissue Remodeling and Polyp Formation In Crsmentioning

confidence: 94%

Immunopathogenesis of Chronic Rhinosinusitis and Nasal Polyposis

Schleimer

2017

Annu. Rev. Pathol. Mech. Dis.

411

419

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Chronic rhinosinusitis (CRS) is a troublesome, chronic inflammatory disease that affects over 10% of the adult population, causing decreased quality of life, lost productivity, and lost time at work and leading to more than a million surgical interventions annually worldwide. The nose, paranasal sinuses, and associated lymphoid tissues play important roles in homeostasis and immunity, and CRS significantly impairs these normal functions. Pathogenic mechanisms of CRS have recently become the focus of intense investigations worldwide, and significant progress has been made. The two main forms of CRS that have been long recognized, with and without nasal polyps, are each now known to be heterogeneous, based on underlying mechanism, geographical location, and race. Loss of the immune barrier, including increased permeability of mucosal epithelium and reduced production of important antimicrobial substances and responses, is a common feature of many forms of CRS. One form of CRS with polyps found worldwide is driven by the cytokines IL-5 and IL-13 coming from Th2 cells, type 2 innate lymphoid cells, and probably mast cells. Type 2 cytokines activate inflammatory cells that are implicated in the pathogenic mechanism, including mast cells, basophils, and eosinophils. New classes of biological drugs that block the production or action of these cytokines are making important inroads toward new treatment paradigms in polypoid CRS.

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Section: Tissue Remodeling and Polyp Formation In Crsmentioning

confidence: 94%

Immunopathogenesis of Chronic Rhinosinusitis and Nasal Polyposis

Schleimer

2017

Annu. Rev. Pathol. Mech. Dis.

411

419

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“…Mucosal epithelial barrier disruption is observed in models of allergic rhinitis and in patients 37 . Allergens can contain proteases and have been shown to disrupt epithelial tight junctions 38, 39 .…”

Section: Barrier Defects In Type 2 Diseasesmentioning

confidence: 99%

“…Using air-liquid interface epithelial cultures, Soyka et al showed reduced barrier function using tissues collected from patients with or without CRS 46 . A number of studies have focused on the loss of epithelial tight junctions in CRS patients by assessing levels of individual tight junction proteins 37, 47 . Alterations of expression of ZO-1 and E-cadherin were reported by Jang et al 48 .…”

Section: Barrier Defects In Type 2 Diseasesmentioning

confidence: 99%

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Etiology of epithelial barrier dysfunction in patients with type 2 inflammatory diseases

Schleimer

Berdnikovs

2017

Journal of Allergy and Clinical Immunology

143

122

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Epithelial barriers of the skin, gastrointestinal tract and airway serve common critical functions such as maintaining a physical barrier against environmental insults and allergens, as well as providing a tissue interface balancing the communication between the internal and external environments. We now understand that in allergic disease, regardless of tissue location, the homeostatic balance of the epithelial barrier is skewed towards loss of differentiation, reduced junctional integrity and impaired innate defense. Importantly, epithelial dysfunction characterized by these traits appears to pre-date atopy and development of allergic disease. Despite our growing appreciation of the centrality of barrier dysfunction in the initiation of allergic disease, many important questions remain to be answered regarding the mechanisms disrupting the normal barrier function. Although our external environment (proteases, allergens, injury) is classically thought of as a principal contributor to barrier disruption associated with allergic sensitization, there is a need to better understand contributions of the internal environment (hormones, diet, circadian clock). Systemic drivers of disease, such as alterations of the endocrine system, metabolism and aberrant control of developmental signaling, are emerging as new players in driving epithelial dysfunction and allergic predisposition at various barrier sites. Identifying such central mediators of epithelial dysfunction, using both systems biology tools and causality-driven laboratory experimentation, will be essential in building new strategic interventions to prevent or reverse the process of barrier loss in allergy.

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“…The epithelial barrier is the first line of defense; its breakdown can play a significant role in allowing external stimuli to enter nasal tissue and provoke immune responses 19. Functional and mechanical defects have been reported in NP.…”

Section: Pathogenesis and Endotypes Of Crsmentioning

confidence: 99%

Emerging Endotypes of Chronic Rhinosinusitis and Its Application to Precision Medicine

Kim

Cho

2017

Allergy Asthma Immunol Res

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Chronic rhinosinusitis (CRS) is a heterogeneous inflammatory disease with various underlying pathophysiologic mechanisms which translate to endotypes, in contrast to clinical phenotypes or histological subtypes. Defining endotypes can help clinicians predict disease prognosis, select subjects suitable for a specific therapy, and assess risks for comorbid conditions, including asthma. Therefore, with recent advancement of biologicals in CRS clinical trials, endotyping can be a breakthrough in treating recalcitrant CRS. CRS is caused by dysregulated immunologic responses to external stimuli, which induce various inflammatory mediators from inflammatory cells, including innate lymphoid cells (ILCs) and T lymphocytes as well as epithelial cells. Thymic stromal lymphopoietin (TSLP), interleukin (IL)-25, and IL-33, which are mainly secreted by epithelial cells in response to external stimuli, act on type 2 ILCs and T helper 2 (Th2) cells, inducing IL-4, IL-5, and IL-13. Local immunoglobulin E (IgE) production is also a signature event in nasal polyps (NP). These inflammatory mediators are novel potential therapeutic targets for recalcitrant CRS. This article reviews recent publications regarding endotypes and endotype-based therapeutic strategies in CRS and NP.

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Barrier function of the nasal mucosa in health and type‐2 biased airway diseases

Abstract: The mucosal lining of the upper airways represents the outer surface

Cited by 109 publications

References 110 publications

Immunopathogenesis of Chronic Rhinosinusitis and Nasal Polyposis

Immunopathogenesis of Chronic Rhinosinusitis and Nasal Polyposis

Etiology of epithelial barrier dysfunction in patients with type 2 inflammatory diseases

Emerging Endotypes of Chronic Rhinosinusitis and Its Application to Precision Medicine

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