Damage‐associated molecular patterns stimulate interleukin‐33 expression in nasal polyp epithelial cells

Paris, Gina; Pozharskaya, Tatyana; Asempa, Tomefa E; Lane, Andrew P.

doi:10.1002/alr.21237

Cited by 45 publications

(33 citation statements)

References 47 publications

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“…Human NECs and sinonasal mucosa were obtained from nasal brushings, and tissue was removed during endoscopic sinus surgery from control and patients with nasal polyps as previously described (39). The research protocol was approved through the Johns Hopkins Institutional Review process, and all patients gave signed informed consent.…”

Section: Methodsmentioning

confidence: 99%

Dysregulated invertebrate tropomyosin–dectin-1 interaction confers susceptibility to allergic diseases

et al. 2018

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The key factors underlying the development of allergic diseases—the propensity for a minority of individuals to develop dysfunctional responses to harmless environmental molecules—remain undefined. We report a pathway of immune counter-regulation that suppresses the development of aeroallergy and shrimp-induced anaphylaxis. In mice, signaling through epithelially expressed dectin-1 suppresses the development of type 2 immune responses through inhibition of interleukin-33 (IL-33) secretion and the subsequent recruitment of IL-13–producing innate lymphoid cells. Although this homeostatic pathway is functional in respiratory epithelial cells from healthy humans, it is dramatically impaired in epithelial cells from asthmatic and chronic rhinosinusitis patients, resulting in elevated IL-33 production. Moreover, we identify an association between a single-nucleotide polymorphism (SNP) in the dectin-1 gene loci and reduced pulmonary function in two cohorts of asthmatics. This intronic SNP is a predicted eQTL (expression quantitative trait locus) that is associated with reduced dectin-1 expression in human tissue. We identify invertebrate tropomyosin, a ubiquitous arthropod-derived molecule, as an immunobiologically relevant dectin-1 ligand that normally serves to restrain IL-33 release and dampen type 2 immunity in healthy individuals. However, invertebrate tropomyosin presented in the context of impaired dectin-1 function, as observed in allergic individuals, leads to unrestrained IL-33 secretion and skewing of immune responses toward type 2 immunity. Collectively, we uncover a previously unrecognized mechanism of protection against allergy to a conserved recognition element omnipresent in our environment.

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Section: Methodsmentioning

confidence: 99%

Dysregulated invertebrate tropomyosin–dectin-1 interaction confers susceptibility to allergic diseases

et al. 2018

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“…SNECs were cultured at the air‐liquid interface (ALI) as described by our group . Epithelial cells were isolated from tissue samples by enzymatic digestion and grown in culture on 10‐mm culture dishes.…”

Section: Methodsmentioning

confidence: 99%

Nuclear erythroid 2‐related factor 2 activation inhibits house dust mite–induced sinonasal epithelial cell barrier dysfunction

London

Tharakan

Lane

et al. 2017

Int Forum Allergy Rhinol

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“…SNECs were cultured at the air‐liquid interface (ALI) cultures, as described by our group . Epithelial cells were isolated from tissue samples by enzymatic digestion and grown in cell culture.…”

Section: Methodsmentioning

confidence: 99%

Reversal of cigarette smoke extract‐induced sinonasal epithelial cell barrier dysfunction through Nrf2 Activation

Tharakan

Halderman

Lane

et al. 2016

Int Forum Allergy Rhinol

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Background Environmental factors such as inhaled pollutants like cigarette smoke may play a significant role in diseases of the upper airway including chronic rhinosinusitis (CRS). Recent studies have shown that cigarette smoke causes impaired airway epithelial cell barrier function likely through environmental oxidative stress related pathways. The purpose of this study is to explore whether enhancing Nrf2, the body’s master antioxidant system, can ameliorate cigarette smoke induced sinonasal epithelial cell barrier dysfunction. Methods Human Sinonasal epithelial cells (HSNECs) were grown from control patients at the air-liquid interface. HSNECs were stimulated with cigarette smoke extract (CSE) with and without pharmacologic activation of Nrf2. HSNECs were then stained for the epithelial cell junctional proteins ZO-1 and JAM-A using confocal microscopy. In addition trans-epithelial electrical resistance (TER) was measured in cultures before and after stimulation with CSE Results CSE stimulation caused a global disruption of the epithelial junctional proteins ZO-1 and JAM-A along with an associated decrease in TER levels. Enhancing Nrf2 levels prior to stimulation with CSE was associated with increased localization of ZO-1 and JAM-A levels at the cell surface and statistically significant increases in TER levels. Conclusions This is the first study to demonstrate that cigarette smoke induced sinonasal epithelial cell barrier dysfunction is reversible by Nrf2 activation. The Nrf2 antioxidant pathway may represent a potential therapeutic target for cigarette smoke associated sinonasal inflammation.

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Damage‐associated molecular patterns stimulate interleukin‐33 expression in nasal polyp epithelial cells

Cited by 45 publications

References 47 publications

Dysregulated invertebrate tropomyosin–dectin-1 interaction confers susceptibility to allergic diseases

Dysregulated invertebrate tropomyosin–dectin-1 interaction confers susceptibility to allergic diseases

Nuclear erythroid 2‐related factor 2 activation inhibits house dust mite–induced sinonasal epithelial cell barrier dysfunction

Reversal of cigarette smoke extract‐induced sinonasal epithelial cell barrier dysfunction through Nrf2 Activation

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