IL33: Roles in Allergic Inflammation and Therapeutic Perspectives

Chan, Ben Chung Lap; Lam, Christopher Wai‐Kei; Tam, Lai‐Shan; Wong, Chun Kwok

doi:10.3389/fimmu.2019.00364

Cited by 231 publications

(183 citation statements)

References 133 publications

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“…Upon epithelial or endothelial injury, IL-33 is released from damaged cells and induces type-2 innate immunity via activation of group 2 innate lymphoid cells (ILC2s) through its receptor ST2. Activated ILC2s produce Th2 cytokines, IL-5, and IL-13, in a synergistic manner (Chan et al, 2019). IL-5 and IL-13 have been reported to stimulate eosinophil activation and induce eosinophilia and ciliated epithelial cell hypertrophy in the respiratory tissue (Schmid-Grendelmeier et al, 2002;Takatsu and Nakajima, 2008;Tanabe et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

Effects of Cigarette Smoke on the Nasal Respiratory and Olfactory Mucosa in Allergic Rhinitis Mice

Ueha

Kondo

et al. 2020

Front. Neurosci.

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Objective: Cigarette smoke (CS) exposure reportedly enhances allergic airway inflammation. However, some studies have shown an association between current cigarette smoke exposure and a low risk for allergic rhinitis. Thus, the impact of CS exposure on allergic rhinitis remains poorly understood. The purpose of this study was to investigate the effects of CS on the respiratory mucosa (RM) and the olfactory epithelium (OE) of mice with allergic rhinitis, as the effects may differ depending on the nasal histological compartments.Methods: Eight-week-old male BALB/c mice were used for this study. We developed a mouse model of smoking by intranasally administering 10 doses of a CS solution (CSS), and a mouse model of allergic rhinitis by sensitization with intraperitoneal ovalbumin (OVA) injection and intranasal challenge with OVA. We examined the effects of CS on the nasal RM and OE in mice with or without allergic rhinitis using histological, serum, and genetic analyses. First, we examine whether CSS exposure induces allergic responses and then, examined allergic responses in the OVA-sensitized allergic rhinitis mice with or without CSS exposure.Results: Short-term CSS administration intensified allergic responses including increased infiltration of eosinophils and inflammatory cells and upregulation of interleukin-5 expression in the nasal RM of OVA-immunized mice, although only CSS induced neither allergic responses nor impairment of the RM and OE. Notably, repetitive OVA-immunization partially impaired the OE in the upper-lateral area, but CSS administration did not reinforce this impairment in OVA-induced allergic mice.Conclusion: Short-term CSS exposure strengthened allergic responses in the nasal RM and did not change the structure of the OE. These results suggest that patients with allergic rhinitis could experience exacerbation of allergic symptoms after CS exposure.

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Section: Discussionmentioning

confidence: 99%

Effects of Cigarette Smoke on the Nasal Respiratory and Olfactory Mucosa in Allergic Rhinitis Mice

Ueha

Kondo

et al. 2020

Front. Neurosci.

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“…However, the functional role of IL-33 in LVV patients is unknown. IL-33 is a key regulator of immune responses shown to license innate and adaptive immunity 18,19 .…”

Section: Discussionmentioning

confidence: 99%

Immunomodulatory role of Interleukin-33 in large vessel vasculitis

Cacoub

Leroyer

Tellier

et al. 2020

Sci Rep

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The mechanisms regulating inflammation in large vessels vasculitis (LVV) are poorly understood. Interleukin 33 (IL-33) has been shown to license innate and adaptive immunity by enhancing Th2 cytokines production. We aimed to examine the role of IL-33 in the immunomodulation of T cell activation in LVV. T cell homeostasis and cytokines production were determined in peripheral blood from 52 patients with giant cell arteritis (GCA) and 50 healthy donors (HD), using Luminex assay, flow cytometry, quantitative RT-PCR and by immunofluorescence analysis in inflammatory aorta lesions. We found increased level of IL-33 and its receptor ST2/IL-1R4 in the serum of patient with LVV. Endothelial cells were the main source of IL-33, whereas Th2 cells, Tregs and mast cells (MC) express ST2 in LVV vessels. IL-33 had a direct immunomodulatory impact by increasing Th2 and Tregs. IL-33 and MC further enhanced Th2 and regulatory responses by inducing a 6.1 fold increased proportion of Tregs (p = 0.008). Stimulation of MC by IL-33 increased indoleamine 2 3-dioxygenase (IDO) activity and IL-2 secretion. IL-33 mRNA expression was significantly correlated with the expression of IL-10 and TGF-β within aorta inflammatory lesions. To conclude, our findings suggest that IL-33 may exert a critical immunoregulatory role in promoting Tregs and Th2 cells in LVV.

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“…Activated mast cells, particularly chymase and tryptase positive connective tissue mast cells, release large amounts of CPA3. Interestingly, IL1RL1 is not only present on granulocytes but also expressed constitutively by mast cells and its ligand, IL-33, stimulates mast cell adhesion to laminin, fibronectin, and vitronectin, and mast cell survival, growth, development, and maturation (32). In addition, mast cell-derived tryptase and chymase cleave IL-33 to generate mature active forms (32).…”

Section: Mast Cells Reside In the Airways And Other Organs And Impactmentioning

confidence: 99%

“…Interestingly, IL1RL1 is not only present on granulocytes but also expressed constitutively by mast cells and its ligand, IL-33, stimulates mast cell adhesion to laminin, fibronectin, and vitronectin, and mast cell survival, growth, development, and maturation (32). In addition, mast cell-derived tryptase and chymase cleave IL-33 to generate mature active forms (32). Together, these data suggest that mast cells represent a major target for ICS in ICS-sensitive COPD patients.…”

Section: Mast Cells Reside In the Airways And Other Organs And Impactmentioning

confidence: 99%

Novel Type 2-high gene clusters associated with corticosteroid sensitivity in COPD

Faiz

Pavlidis

Kuo

et al. 2020

Preprint

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RationaleSevere asthma and COPD share common pathophysiologic traits such as relative corticosteroid insensitivity. We recently published three transcriptome-associated clusters (TACs) using hierarchical analysis of the sputum transcriptome in asthmatics from the U-BIOPRED cohort with one Type 2-high signature (TAC1) and 2 Type 2-low signatures. ObjectiveWe examined whether gene-expression signatures obtained in asthma can be used to identify the subgroup of COPD patients with steroid sensitivity. MethodsUsing gene set variation analysis (GSVA), we examined the distribution and enrichment scores (ES) of the 3 TACs in the transcriptome of bronchial biopsies from 46 patients who participated in the GLUCOLD COPD study that received 30 months of treatment with inhaled corticosteroids (ICS) with and without an added long-acting β-agonist (LABA). The identified signatures were then associated with longitudinal clinical variables after treatment. Measurements and main resultsBronchial biopsies in COPD patients at baseline showed a wide range of expression of the 3 TACs. After ICS±LABA treatment, the ES of TAC1 was significantly reduced at 30 months, but those of TAC2 and TAC3 were unaffected. A corticosteroid-sensitive TAC1 (sub)signature was developed from the TAC1 ICS-responsive genes. This signature consisted of mast cellspecific genes identified by single-cell RNA-seq and positively correlated with bronchial biopsy mast cell numbers following ICS±LABA. Baseline levels of gene transcription predicted change in FEV1 %predicted following 30-month ICS±LABA. ConclusionsSputum-derived transcriptomic signatures from an asthma cohort can be recapitulated in bronchial biopsies of COPD patients and identified airway wall mast cells as a predictor of those COPD patients who will benefit from inhaled corticosteroids.Abbreviations: FEV 1 = Forced Expiratory Volume in 1second and RV/TLC= residual volume/total lung capacity .

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IL33: Roles in Allergic Inflammation and Therapeutic Perspectives

Cited by 231 publications

References 133 publications

Effects of Cigarette Smoke on the Nasal Respiratory and Olfactory Mucosa in Allergic Rhinitis Mice

Effects of Cigarette Smoke on the Nasal Respiratory and Olfactory Mucosa in Allergic Rhinitis Mice

Immunomodulatory role of Interleukin-33 in large vessel vasculitis

Novel Type 2-high gene clusters associated with corticosteroid sensitivity in COPD

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