Targeting the Epithelium-Derived Innate Cytokines: From Bench to Bedside

Ham, Jongho; Shin, Jae Woo; Ko, Byeong Cheol; Kim, Hye Young

doi:10.4110/in.2022.22.e11

Cited by 19 publications

(22 citation statements)

References 158 publications

(207 reference statements)

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“…Exposing the HT-29 cell line, as IEC, to ovalbumin enhanced secretion of type 2 driving alarmins. Contributions of these alarmins in modulating DC function enabling them to drive Th2 cell development have been previously studied ( 4 , 17 – 19 ). Murine studies revealed that increased epithelial IL33 secretion is sufficient for in vivo DC activation leading to peanut allergy, independent of IL25 and TSLP ( 17 ).…”

Section: Discussionmentioning

confidence: 99%

An advanced in vitro human mucosal immune model to predict food sensitizing allergenicity risk: A proof of concept using ovalbumin as model allergen

et al. 2023

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BackgroundThe global demand of sustainable food sources leads to introduction of novel foods on the market, which may pose a risk of inducing allergic sensitization. Currently there are no validated in vitro assays mimicking the human mucosal immune system to study sensitizing allergenicity risk of novel food proteins. The aim of this study was to introduce a series of sequential human epithelial and immune cell cocultures mimicking key immune events after exposure to the common food allergen ovalbumin from intestinal epithelial cell (IEC) activation up to mast cell degranulation.MethodsThis in vitro human mucosal food sensitizing allergenicity model combines crosstalk between IEC and monocyte-derived dendritic cells (moDC), followed by coculture of the primed moDCs with allogenic naïve CD4+ T cells. During subsequent coculture of primed CD4+ T cells with naïve B cells, IgE isotype-switching was monitored and supernatants were added to primary human mast cells to investigate degranulation upon IgE crosslinking. Mediator secretion and surface marker expression of immune cells were determined.ResultsOvalbumin activates IEC and underlying moDCs, both resulting in downstream IgE isotype-switching. However, only direct exposure of moDCs to ovalbumin drives Th2 polarization and a humoral B cell response allowing for IgE mediated mast cell degranulation, IL13 and IL4 release in this sequential DC-T cell-B cell-mast cell model, indicating also an immunomodulatory role for IEC.ConclusionThis in vitro coculture model combines multiple key events involved in allergic sensitization from epithelial cell to mast cell, which can be applied to study the allergic mechanism and sensitizing capacity of proteins.

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Section: Discussionmentioning

confidence: 99%

An advanced in vitro human mucosal immune model to predict food sensitizing allergenicity risk: A proof of concept using ovalbumin as model allergen

et al. 2023

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“…Specifically, inhaled allergens disrupt the airway epithelium, which increases the production of alarmins, stimulating T helper (Th) 2 cells, type 2 innate lymphoid cells (ILC2s), eosinophils, and alveolar macrophages. 19 The local and systemic augmentation of eosinophils is considered a key risk factor for asthma exacerbation. 20 However, 10%–33% of asthmatics have normal ranges of serum immunoglobulin E (IgE) and a non-allergic phenotype that is less responsive to standard therapy 21 22 and is marked by increased neutrophilic inflammation.…”

Section: Neutrophils In Chronic Respiratory Diseasesmentioning

confidence: 99%

The Dynamic Contribution of Neutrophils in the Chronic Respiratory Diseases

Ham

Kim

et al. 2022

Allergy Asthma Immunol Res

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Asthma, chronic obstructive pulmonary disease, and idiopathic pulmonary fibrosis are representative chronic respiratory diseases (CRDs). Although they differ in terms of disease presentation, they are all thought to arise from unresolved inflammation. Neutrophils are not only the first responders to acute inflammation, but they also help resolve the inflammation. Notably, emerging clinical studies show that CRDs are associated with systemic and local elevation of neutrophils. Moreover, murine studies suggest that airway-infiltrating neutrophils not only help initiate airway inflammation but also prolong the inflammation. Given this background, this review describes neutrophil-mediated immune responses in CRDs and summarizes the completed, ongoing, and potential clinical trials that test the therapeutic value of targeting neutrophils in CRDs. The review also clarifies the importance of understanding how neutrophils interact with other immune cells and how these interactions contribute to chronic inflammation in specific CRDs. This information may help identify future therapeutic strategies for CRDs.

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“…Similarly, airway exposure to the common fungal aeroallergen Alternaria alternata upregulates IL-33, IL-5, and IL-13 levels in the bronchoalveolar lavage of mice and induces eosinophilic airway inflammation, however, this inflammation does not develop when the mice lack IL-33 or ILC2s ( 56 , 57 ). Thus, allergens elevate epithelial-cell secretion of alarmins, which activate ILC2s in the lung, which in turn leads to the pathological effects of allergic asthma, namely, eosinophil infiltration, AHR, and mucus overproduction ( 58 – 61 ).…”

Section: Innate Lympoid Cells In Asthmamentioning

confidence: 99%

Memory-like innate lymphoid cells in the pathogenesis of asthma

et al. 2022

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Innate lymphoid cells (ILCs) are recently discovered innate immune cells that reside and self-renew in mucosal tissues and serve as the first line of defense against various external insults. They include natural killer (NK) cells, ILC1s, ILC2s, ILC3s, and lymphoid tissue inducer cells. The development and functions of ILC1–3 reflect those of their adaptive immunity TH1, TH2, and TH17 T-cell counterparts. Asthma is a heterogeneous disease caused by repeated exposure to specific allergens or host/environmental factors (e.g., obesity) that stimulate pathogenic pulmonary immune cells, including ILCs. Memory used to be a hallmark of adaptive immune cells until recent studies of monocytes, macrophages, and NK cells showed that innate immune cells can also exhibit greater responses to re-stimulation and that these more responsive cells can be long-lived. Besides, a series of studies suggest that the tissue-resident innate lymphoid cells have memory-like phenotypes, such as increased cytokine productions or epigenetic modifications following repetitive exposure to allergens. Notably, both clinical and mouse studies of asthma show that various allergens can generate memory-like features in ILC2s. Here, we discuss the biology of ILCs, their roles in asthma pathogenesis, and the evidence supporting ILC memory. We also show evidence suggesting memory ILCs could help drive the phenotypic heterogeneity in asthma. Thus, further research on memory ILCs may be fruitful in terms of developing new therapies for asthma.

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Targeting the Epithelium-Derived Innate Cytokines: From Bench to Bedside

Cited by 19 publications

References 158 publications

An advanced in vitro human mucosal immune model to predict food sensitizing allergenicity risk: A proof of concept using ovalbumin as model allergen

An advanced in vitro human mucosal immune model to predict food sensitizing allergenicity risk: A proof of concept using ovalbumin as model allergen

The Dynamic Contribution of Neutrophils in the Chronic Respiratory Diseases

Memory-like innate lymphoid cells in the pathogenesis of asthma

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