Der p 38 Is a Bidirectional Regulator of Eosinophils and Neutrophils in Allergy

Hong, Min; Kashif, Ayesha; Kim, Geunyeong; Park, Beom Seok; Lee, Na Rae; Yang, Eun Ju; Mun, Ji Young; Choi, Hyosun; Kim, Sang Hoon; Kim, Hyun Jik; Lee, Soo Jin; Lee, Jisook; Hong, Yujin; Kim, In Sik

doi:10.4049/jimmunol.2001144

Cited by 8 publications

(3 citation statements)

References 48 publications

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“…Even though the effect was rather weak, we could detect a small reduction in the frequency of eosinophils and an increase of neutrophils. Since HDM extracts contain various allergens which trigger allergic responses via different pathways leading to eosinophilic and/or neutrophilic infiltration ( 71 – 74 ), it will be interesting in the future to further decipher in which of these reactions the immunoproteasome is involved.…”

Section: Discussionmentioning

confidence: 99%

Immunoproteasome Inhibition Reduces the T Helper 2 Response in Mouse Models of Allergic Airway Inflammation

et al. 2022

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BackgroundAllergic asthma is a chronic disease and medical treatment often fails to fully control the disease in the long term, leading to a great need for new therapeutic approaches. Immunoproteasome inhibition impairs T helper cell function and is effective in many (auto-) inflammatory settings but its effect on allergic airway inflammation is unknown.MethodsImmunoproteasome expression was analyzed in in vitro polarized T helper cell subsets. To study Th2 cells in vivo acute allergic airway inflammation was induced in GATIR (GATA-3-vYFP reporter) mice using ovalbumin and house dust mite extract. Mice were treated with the immunoproteasome inhibitor ONX 0914 or vehicle during the challenge phase and the induction of airway inflammation was analyzed.ResultsIn vitro polarized T helper cell subsets (Th1, Th2, Th17, and Treg) express high levels of immunoproteasome subunits. GATIR mice proved to be a useful tool for identification of Th2 cells. Immunoproteasome inhibition reduced the Th2 response in both airway inflammation models. Furthermore, T cell activation and antigen-specific cytokine secretion was impaired and a reduced infiltration of eosinophils and professional antigen-presenting cells into the lung and the bronchoalveolar space was observed in the ovalbumin model.ConclusionThese results show the importance of the immunoproteasome in Th2 cells and airway inflammation. Our data provides first insight into the potential of using immunoproteasome inhibition to target the aberrant Th2 response, e.g. in allergic airway inflammation.

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Section: Discussionmentioning

confidence: 99%

Immunoproteasome Inhibition Reduces the T Helper 2 Response in Mouse Models of Allergic Airway Inflammation

et al. 2022

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“…In an inflammatory state, NRG-1 exhibits a protective effect that reduces IL-6, IL-8, and MCP-1, which connects with the reversal of neutrophil apoptosis decreased by TNF-α and IFN-γ. Previous studies have reported the close relation of allergy with cytokine secretion and neutrophil apoptosis (Hong et al, 2021;Jeon et al, 2021). Based on these findings, NRG-1 may play a critical role in the protection of exacerbations of allergies as well as other inflammatory diseases.…”

Section: Acknowledgementmentioning

confidence: 91%

Anti-inflammatory Effects of Neuregulin-1 via the Downregulation of IL-6, IL-8, and MCP-1 Secretion

Lee

2022

Biomed Sci Letters

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The trophic factor Neuregulin-1 (NRG-1) plays a critical role in the development of the peripheral nervous system and the repair of nerve injuries. The regulation of neutrophil apoptosis by cytokine secretion from structural cells is an important process in inflammatory diseases, including asthma. This study aimed to investigate the relationship between NRG-1 and the alteration of neutrophil apoptosis by the regulation of cytokine release in the human lung epithelial BEAS-2B cells. Tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) induce the increase in the release of interleukin (IL)-6, IL-8, and monocyte chemoattractant protein-1 (MCP-1). NRG-1 alone had no effect on the secretion of IL-6, IL-8, and MCP-1. However, co-treatment of TNF-α and IFN-γ with NRG-1 inhibited the secretion of IL-6, IL-8, and MCP-1 that had been increased by TNF-α and IFN-γ. Treatment with NRG-1 did not have a direct effect on neutrophil apoptosis. Co-treatment of TNF-α and IFN-γ with NRG-1 was not effective on suppression of neutrophil apoptosis due to TNF-α and IFN-γ. The supernatant of BEAS-2B cells after co-treatment of TNF-α and IFN-γ with NRG-1 suppressed the inhibition of neutrophil apoptosis that had been caused due to the supernatant treated with TNF-α and IFN-γ. Taken together, NRG-1 has an anti-inflammatory effect in an inflammatory milieu by the regulation of cytokine secretion and neutrophil apoptosis.

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“…novel TLR4-binding allergen, which acts as a bidirectional regulator in the transition of predominant eosinophils or/and neutrophils related to asthma severity, and it may be an alternative card in the AIT of HDM allergy. 49,50) A complex combination of current vaccine technologies and an unexpected novel approach will continuously be pursued towards contribution to the development of AIT.…”

Section: A C C E P T E D a R T I C L Ementioning

confidence: 99%

New approaches to immunotherapy in house dust mite allergy

Kim

2023

Clin Exp Pediatr

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Allergen immunotherapy (AIT) has developed over the last few decades and has emerged as a promising treatment. House dust mite is a target allergen in AIT, and various modified house dust mite allergens have been improved for their efficacy. Moreover, clinical trials have proved their significantly therapeutic effects in allergy. This article review focuses on house dust mite allergens developed for AIT efficacy, and determines that their action mechanisms are strongly based on immune tolerance.Treatments for house dust mite allergens have been optimized by modification or/and addition of adjuvants, and clinically evaluated by subcutaneous and sublingual administration. Representative allergens used in AIT are chemically modified allergoids and recombinant allergens, including altered epitopes. The effective mechanisms subsequent to AIT include the suppressive actions of interleukin-10 and transforming growth factor-β secreted by regulatory cells, including regulatory T cells and regulatory B cells, and isotype switching from immunoglobulin E to immunoglobulin G4. Further studies of AIT are needed to achieve the milestone in treating allergies.

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Der p 38 Is a Bidirectional Regulator of Eosinophils and Neutrophils in Allergy

Cited by 8 publications

References 48 publications

Immunoproteasome Inhibition Reduces the T Helper 2 Response in Mouse Models of Allergic Airway Inflammation

Immunoproteasome Inhibition Reduces the T Helper 2 Response in Mouse Models of Allergic Airway Inflammation

Anti-inflammatory Effects of Neuregulin-1 via the Downregulation of IL-6, IL-8, and MCP-1 Secretion

New approaches to immunotherapy in house dust mite allergy

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