Innate responses to pollen allergens

Hosoki, Koa; Boldogh, István; Sur, Sanjiv

doi:10.1097/aci.0000000000000136

Cited by 47 publications

(39 citation statements)

References 91 publications

(120 reference statements)

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“…Pollens and other natural allergens are a complex mixture of proteases, antigens, lipids and oxidases. Proteases can not only damage cell junctions, increasing allergen penetration to dendritic cells, but also induce protease-activated receptor (PAR) signalling in epithelial cells [47]. Increased release of ROS by oxidases or mitochondria forms an important second hit, during this cascade, which is critical for sustained immune response.…”

Section: Mitochondrial Dysfunction and Allergymentioning

confidence: 99%

“…Such mice had greater IgE response with increased airway remodelling and hyperresponsiveness. The mechanistic connections between allergens and mitochondrial dysfunction may take one or more of many parallel paths [47]. Pollens and other natural allergens are a complex mixture of proteases, antigens, lipids and oxidases.…”

Section: Mitochondrial Dysfunction and Allergymentioning

confidence: 99%

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Mitochondrial Function in Allergic Disease

Iyer

Mishra

Agrawal

2017

Curr Allergy Asthma Rep

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Recent research has shown allergy, asthma and metabolic syndrome to be linked to mitochondrial dysfunction. Environmental pollutants and allergens are observed to cause mitochondrial dysfunction, primarily by inducing oxidative stress and ROS production. Malfunctioning mitochondria change the bioenergetics of the cell and its metabolic profile to favour systemic inflammation, which drives all three types of morbidities. Given the existing experimental evidence, approaches targeting mitochondria (e.g. antioxidant therapy and mitochondrial replacement) are being conducted in relevant disease models-with some progressing towards clinical trials, making mitochondrial function the focus of translational therapy research in asthma, allergy and linked metabolic syndrome.

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Section: Mitochondrial Dysfunction and Allergymentioning

confidence: 99%

Section: Mitochondrial Dysfunction and Allergymentioning

confidence: 99%

Mitochondrial Function in Allergic Disease

Iyer

Mishra

Agrawal

2017

Curr Allergy Asthma Rep

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“…Allergen challenge in subjects with asthma or seasonal allergic rhinitis has been reported to stimulate IL-8 secretion (2-4) and neutrophil recruitment (5) to the airways. Pollens contain numerous intrinsic factors that can stimulate an innate immune response (6). We and other have reported that intranasal challenge with pollen extract rapidly recruits neutrophils into the airways of naive mice (5,(7)(8)(9)(10).…”

Section: Clinical Relevancementioning

confidence: 99%

Facilitation of Allergic Sensitization and Allergic Airway Inflammation by Pollen-Induced Innate Neutrophil Recruitment

Hosoki¹,

Aguilera-Aguirre²,

Brasier

et al. 2016

Am J Respir Cell Mol Biol

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Neutrophil recruitment is a hallmark of rapid innate immune responses. Exposure of airways of naive mice to pollens rapidly induces neutrophil recruitment. The innate mechanisms that regulate polleninduced neutrophil recruitment and the contribution of this neutrophilic response to subsequent induction of allergic sensitization and inflammation need to be elucidated. Here we show that ragweed pollen extract (RWPE) challenge in naive mice induces C-X-C motif ligand (CXCL) chemokine synthesis, which stimulates chemokine (C-X-C motif) receptor 2 (CXCR2)-dependent recruitment of neutrophils into the airways. Deletion of Toll-like receptor 4 (TLR4) abolishes CXCL chemokine secretion and neutrophil recruitment induced by a single RWPE challenge and inhibits induction of allergic sensitization and airway inflammation after repeated exposures to RWPE. Forced induction of CXCL chemokine secretion and neutrophil recruitment in mice lacking TLR4 also reconstitutes the ability of multiple challenges of RWPE to induce allergic airway inflammation. Blocking RWPEinduced neutrophil recruitment in wild-type mice by administration of a CXCR2 inhibitor inhibits the ability of repeated exposures to RWPE to stimulate allergic sensitization and airway inflammation. Administration of neutrophils derived from naive donor mice into the airways of Tlr4 knockout recipient mice after each repeated RWPE challenge reconstitutes allergic sensitization and inflammation in these mice. Together these observations indicate that pollen-induced recruitment of neutrophils is TLR4 and CXCR2 dependent and that recruitment of neutrophils is a critical rate-limiting event that stimulates induction of allergic sensitization and airway inflammation. Inhibiting pollen-induced recruitment of neutrophils, such as by administration of CXCR2 antagonists, may be a novel strategy to prevent initiation of pollen-induced allergic airway inflammation.

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“…35,36 It has been shown that activated neutrophils accumulate at the site of allergic provocation and have the ability to prime CD4 + T cells, 37 a crucial event for the initiation of allergic inflammation. Grass pollen extract can induce neutrophil immune responses through the secretion of IL-8, 38,39 reinforcing the importance of this cytokine in the allergic response. We showed here that in TNF-α-stimulated lung epithelial cells, TGFβ1-mim suppressed IL-8 gene expression and cytokine secretion.…”

Section: Il-8 Is a Chemoattractant Cytokine Produced By A Variety Ofmentioning

confidence: 90%

TGFβ1 mimetic peptide modulates immune response to grass pollen allergens in mice

Araújo

Aglas

Vaz

et al. 2019

Allergy

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Background: Transforming growth factor β1 (TGFβ1) is a cytokine that exerts immunosuppressive functions, as reflected by its ability to induce regulatory T (Treg) cell differentiation and inhibit Th1 and Th2 responses. Hence, peptides that mimic the active core domain of TGFβ1 may be promising candidates for modulation of the allergic response. This study aimed to investigate a synthetic TGFβ1 mimetic peptide (TGFβ1-mim) for its ability to modulate the immune response during allergic sensitization to grass pollen allergens. Methods:The in vitro action of TGFβ1-mim was evaluated in human lung epithelial cells, Jurkat cells, and rat basophilic leukemia cells. The in vivo action was evaluated in a murine model of Phl p 5 allergic sensitization. Additionally, the Th2 modulatory response was evaluated in IL-4 reporter mice. Results:In vitro, TGFβ1-mim downregulated TNF-α production, IL-8 gene expression, and cytokine secretion, upregulated IL-10 secretion, and inhibited Phl p 5-induced basophil degranulation. During Phl p 5 sensitization in mice, TGFβ1-mim downregulated IL-2, IL-4, IL-5, IL-13, and IFN-γ, upregulated IL-10, and induced Treg cell production. Furthermore, mice treated with TGFβ1-mim had lower levels of IgE, IgG1, IgG2a and higher levels of IgA antibodies than control mice. In a reporter mouse, the mimetic inhibited Th2 polarization. Conclusion:The TGFβ1-mim efficiently modulated various important events that exacerbate the allergic microenvironment, including the production of main cytokines that promote Th1 and Th2 differentiation, and the induction of allergen-specific regulatory T cells, highlighting its potential use in therapeutic approaches to modulate the immune response toward environmental allergens. K E Y W O R D S allergic sensitization, grass pollen allergy, immune regulation, immunotherapy, TGFβ1This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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Innate responses to pollen allergens

Cited by 47 publications

References 91 publications

Mitochondrial Function in Allergic Disease

Mitochondrial Function in Allergic Disease

Facilitation of Allergic Sensitization and Allergic Airway Inflammation by Pollen-Induced Innate Neutrophil Recruitment

TGFβ1 mimetic peptide modulates immune response to grass pollen allergens in mice

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