Sentinels at the wall: epithelial‐derived cytokines serve as triggers of upper airway type 2 inflammation

Patel, Neil N.; Kohanski, Michael A.; Maina, Ivy W.; Workman, Alan D.; Herbert, De’Broski R.; Cohen, Noam A.

doi:10.1002/alr.22206

Cited by 36 publications

(21 citation statements)

References 83 publications

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“…Secreted IL‐33 functions as an alarm in warning endothelial and epithelial damage, apoptosis, and necrosis. The binding of IL‐33 to ST2 results in the recruitment of IRAK, IRAK4, MyD88, and TRAF6 to ST2 to activate NF‐kB and MAP kinases, ultimately initiating its pro‐inflammatory effects 32,49 . An altered subcellular localization of IL‐33 can dramatically affect immune homeostasis, supporting the notion that the sequestration of IL‐33 in the nucleus is to limit its pro‐inflammatory potential 59 .…”

Section: Epithelium‐derived Il‐33mentioning

confidence: 88%

“…With Toll‐like receptors (TLR) and nucleotide‐binding oligomerization domain (NOD)–like receptors (NLR) expressed on the surface, epithelial cells can recognize structurally conservative pathogen‐associated molecular patterns (PAMPs) in pathogens and respond to these exogenous danger signals by eliciting immune responses. The important response of the epithelium to the PAMP‐TLR/NLR interaction is the secretion of various cytokines, especially IL‐25, IL‐33, and TSLP, which can induce both innate and adaptive immune responses and lean inflammations toward a type 2 immune response bias 10,32 …”

Section: Introductionmentioning

confidence: 99%

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Role of IL‐25, IL‐33, and TSLP in triggering united airway diseases toward type 2 inflammation

Hong

Liao

Chen

et al. 2020

Allergy

134

107

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Under the concept of "united airway diseases," the airway is a single organ wherein upper and lower airway diseases are commonly comorbid. The upper and lower airways are lined with respiratory epithelium that plays a vital role in immune surveillance and modulation as the first line of defense to various infective pathogens, allergens, and physical insults. Recently, there is a common hypothesis emphasizing epithelium‐derived cytokines, namely IL‐25, IL‐33, and TSLP, as key regulatory factors that link in immune‐pathogenic mechanisms of allergic rhinitis (AR), chronic rhinosinusitis (CRS), and asthma, mainly involving in type 2 inflammatory responses and linking innate and adaptive immunities. Herein, we review studies that elucidated the role of epithelium‐derived triple cytokines in both upper and lower airways with the purpose of expediting better clinical treatments and managements of AR, CRS, asthma, and other associated allergic diseases via applications of the modulators of these cytokines.

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Section: Epithelium‐derived Il‐33mentioning

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Role of IL‐25, IL‐33, and TSLP in triggering united airway diseases toward type 2 inflammation

Hong

Liao

Chen

et al. 2020

Allergy

134

107

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“…Unexpectedly, as shown in Supplementary data 2, these cytokines were dramatically inhibited but not increased by LPS. The epithelia-derived cytokines TSLP, IL-25 and IL-33, which could promote asthmatic inflammation by driving Th2 responses [28,29] were also suppressed by LPS. In addition, mRNA level of GATA-3 and ID2, the transcriptional factors related to Th2 cytokines were consistently decreased by LPS.…”

Section: Discussionmentioning

confidence: 99%

LPS aggravates lung inflammation induced by RSV by promoting the ERK-MMP-12 signaling pathway in mice

et al. 2020

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Background: RSV can lead to persistent airway inflammation and airway hyperresponsiveness (AHR), and is intimately associated with childhood recurrent wheezing and asthma, but the underlying mechanisms remain unclear. Lipopolysaccharide (LPS) is also implicated in the onset and exacerbation of asthma. However, whether inhalation of LPS can boost airway inflammation induced by RSV is not clear. In this study, we utilized an LPS-and RSV-superinfected mouse model to explore underlying pathogenesis. Methods: Mice were infected with RSV on day 0 and inoculated with LPS from day 35 to day 41, samples were collected on day 42. Inflammatory cells, lung histopathology and AHR were measured. Cytokines were detected by ELISA and ERK, JNK, p38 was determined by western blot. MMP408, PD98059, SP600125 and SB203580 were used to inhibit MMP-12, ERK, JNK and p38 respectively. Results: LPS exposure superimposed on RSV-infected lungs could lead to more vigorous cellular influx, lung structures damage, augmented AHR and higher MMP-12 levels. Inhibition of MMP-12 or ERK signaling pathway in vivo both diminished LPS-driven airway inflammation and AHR. Conclusions: Exposure to LPS in RSV-infected mice is associated with enhanced increases in ERK-MMP-12 expression that translates into increased lung inflammation and AHR. These findings contribute novel information to the field investigating the onset of post-RSV bronchiolitis recurrent wheezing as a result of LPS exposure.

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“…These are primarily epithelial-derived cytokines, in particular, interleukin 25 (IL-25), thymic stromal lymphopoietin (TSLP), and interleukin 33 (IL-33). 47 Such mediators stimulate innate lymphoid cells to release IL-13 and IL-5, 48 and induce T-Helper 9 cells to produce IL-9, a mast cell growth factor able to promote their IgE-mediated activation. 49 The alarmin IL-33 can activate lymphoid type 2 interstitial cells (ILC2) which in turn induce the production of IL-13 and IL-4.…”

Section: Med Iator S Involved In Food Allergymentioning

confidence: 99%

The use of biologics in food allergy

Fiocchi

Vickery

Wood

2021

Clin Experimental Allergy

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Background Food allergy continues to pose problems due to its increased frequency and its increasingly high severity. In this context, alongside the traditional avoidance strategies of allergenic foods and desensitization through the cautious progression of exposure to foods in the context of oral immunotherapy (OIT), alternative strategies have made their way in the last decades. We review the possibilities of intervention in food allergy with the use of biological drugs capable of interfering with the synthesis of IgE, with their mechanisms of action, or with complex biological mechanisms that lead to the establishment of a food allergy. Methods Repeated Entrez PubMed searches using the template algorithm “Food allergy” and “biologics” or “Omalizumab” or “Dupilumab” or “milk desensitization” or “oral tolerance induction” or “oral immunotherapy” or “Etokimab” or “Tezepelumab” or “Quilizumab” or “Ligelizumab” or “Tralokinumab” or “Nemolizumab” or “Mepolizumab” or “Reslizumab” or “Benralizumab”. The authors’ clinical experience in paediatric allergy units of University hospitals was also drawn upon. Results The landscape in this context has changed dramatically over the past 10 years. We have acquired knowledge mainly on the effect of different types of anti‐IgE treatments in poliallergic patients with food allergy, and in patients treated with OIT. However, other mediators are being targeted by specific biologic treatments. Among them, the alarmins Il‐33 and TSLP, IL‐4 and IL‐13, eosinophil‐related molecules as IL‐6, IL‐8, IL‐10, IL‐12, and mostly IL‐5, and integrins involved in the pathogenesis of eosinophilic gastrointestinal diseases (EGIDs), as SIGLEC‐8. Conclusions The ever‐better knowledge of the mechanisms of food allergy allowing these developments will improve not only the perspective of patients with the most serious immediate food allergies such as anaphylaxis, but also those of patients with related diseases such as atopic dermatitis, eosinophilic esophagitis, and EGIDs. Biologics are also intended to complement OIT strategies that have developed over the years.

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Sentinels at the wall: epithelial‐derived cytokines serve as triggers of upper airway type 2 inflammation

Cited by 36 publications

References 83 publications

Role of IL‐25, IL‐33, and TSLP in triggering united airway diseases toward type 2 inflammation

Role of IL‐25, IL‐33, and TSLP in triggering united airway diseases toward type 2 inflammation

LPS aggravates lung inflammation induced by RSV by promoting the ERK-MMP-12 signaling pathway in mice

The use of biologics in food allergy

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