IL‐37 regulates allergic inflammation by counterbalancing pro‐inflammatory IL‐1 and IL‐33

Schröder, A.; Lunding, Lars; Zissler, Ulrich M.; Vock, Christina; Webering, Sina; Ehlers, Johanna Christine; Orinska, Zane; Chaker, Adam; Schmidt‐Weber, Carsten B.; Lang, Niklas; Schiller, Herbert B.; Mall, Marcus; Fehrenbach, Heinz; Dinarello, Charles A.; Wegmann, Michael

doi:10.1111/all.15072

Cited by 32 publications

(25 citation statements)

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“…Moreover, anti-inflammatory mechanisms should be investigated in the context of ID in future studies. 28,51,52 In conclusion, the upregulation of IL1beta and CXCL8 in immune dysregulation in ID may indicate a bronchiectasis state. Not only inflammatory, but also functional T cell exhaustion could play a role reported by previous studies.…”

Section: Discussionmentioning

confidence: 92%

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Bronchial inflammation biomarker patterns link humoral immunodeficiency with bronchiectasis‐related small airway dysfunction

Zissler

Thron

Eckrich³

et al. 2022

Clin Experimental Allergy

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Background The progression of chronic destructive lung disease in patients with humoral immunodeficiency (ID) and concomitant development of bronchiectasis is difficult to prevent. Lung function tests in these patients typically show bronchial obstruction of the small airways in combination with increased air trapping in the distal airways, which is consistent with small airway dysfunction. Objective The objective was to assess the grade of chronic lower airway inflammation and small airway dysfunction from induced sputum and the corresponding local pro‐inflammatory mediator pattern to discriminate patients affected by bronchiectasis‐related Small Airway Dysfunction (SAD). Methods In a prospective design, 22 patients with ID (14 CVID, 3 XLA, 3 hyper‐IgM syndrome, 1 hyper‐IgE syndrome and low IgG levels due to treatment with rituximab and 1 SCID after BMT and persistent humoral defect) and 21 healthy controls were examined. Lung function, Fraction Expiratory Nitric Oxide (FeNO) and pro‐inflammatory cytokine levels were compared in subsets of patients with (ID + BE) and without bronchiectasis (ID) pre‐stratified using high‐resolution computed tomography (HRCT) scans and control subjects. Results Analysis of induced sputum showed significantly increased total cell counts and severe neutrophilic inflammation in ID. The concomitant SAD revealed higher total cell numbers compared to ID. Bronchial inflammation in ID is clearly mirrored by pro‐inflammatory mediators IL‐1β, IL‐6 and CXCL‐8, whilst TNF‐α revealed a correlation with lung function parameters altered in the context of bronchiectasis‐related Small Airway Dysfunction. Conclusions In spite of immunoglobulin substitution, bronchial inflammation was dominated by neutrophils and was highly increased in patients with ID + BE. Notably, the pro‐inflammatory cytokines in patients with ID were significantly increased in induced sputum. The context‐dependent cytokine pattern in relation to the presence of concomitant bronchiectasis associated with SAD in ID patients could be helpful in delimiting ID patient subgroups and individualizing therapeutic approaches.

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Section: Discussionmentioning

confidence: 92%

“…However, these mechanisms need to be further elucidated in a future study resolving the ID‐related inflammation on a single cell level. Moreover, anti‐inflammatory mechanisms should be investigated in the context of ID in future studies 28,51,52 …”

Section: Discussionmentioning

confidence: 99%

Bronchial inflammation biomarker patterns link humoral immunodeficiency with bronchiectasis‐related small airway dysfunction

Zissler

Thron

Eckrich³

et al. 2022

Clin Experimental Allergy

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“…On the other hand, anti-inflammatory factors are indicated to contribute to the maintenance of homeostasis, including IL-10 and IL-37. A thorough understanding of these mechanisms may be a key factor in the therapy, control, and prevention of bronchial asthma [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

Respiratory Symptoms, Allergies, and Environmental Exposures in Children with and without Asthma

Wypych-Ślusarska

Grot

Maria

et al. 2022

IJERPH

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Background: Epidemiological data concerning the level of asthma morbidity indicate that in Poland, asthma is diagnosed in 5–10% of the pediatric population. Aim The purpose of this study was to compare the prevalence of respiratory symptoms and allergies in a group of children with and without asthma and to evaluate the association between exposure to environmental factors and the prevalence of bronchial asthma in a pediatric population. Material and Methods: A cross-sectional study was conducted on a group of 995 children attending primary schools in the province of Silesia in 2018–2019. The research tool was an anonymous questionnaire developed based on the form used in The International Study of Asthma and Allergies in Childhood (ISAAC). Children’s health status, the prevalence of bronchial asthma, and the performance of allergic skin tests were assessed based on parents’ indications in a questionnaire. Environmental exposures such as mold and dampness in apartments or ETS were similarly assessed. Analyses were performed using Statistica 13.0; p < 0.05. Results: A total of 88 subjects (8.8%) suffered from bronchial asthma. Parents of children with asthma, compared to parents of children without the disease, were more likely to rate their children’s health as rather good (43.2% vs. 38.0%) or average (21.6% vs. 3.1%). All analyzed respiratory symptoms, as well as allergies, were statistically more frequent in children with bronchial asthma. Conclusions: The parent’s subjective assessment of the child’s health varied significantly according to the asthma diagnosis. Asthma is also associated with other diseases: allergic reactions to pollen, house dust, hay fever, and AD (atopic dermatitis) were statistically significantly more frequent among children diagnosed with bronchial asthma.

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“…Recent findings highlight that other regulatory factors produced by T and other inflammatory cells play a key role in the efficacy of AIT, in particular IL-35 and IL-37. There are no current studies on the activity of IL-37 during AIT, but due to what is known so far, it is reasonable that this new cytokine may play a role in allergen-specific induced tolerance by reducing IgE, eosinophils, and type 2 response [ 131 , 132 ]. By contrast, data on IL-35 are more promising.…”

Section: Alterations Of Innate and Adaptive Immunity Induced By Aitmentioning

confidence: 99%

How the Immune System Responds to Allergy Immunotherapy

et al. 2022

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IgE-mediated diseases represent a highly diversified and multifactorial group of disorders that can deeply impact the patients’ quality of life. Currently, allergy immunotherapy (AIT) still remains the gold standard for the management of such pathologies. In this review, we comprehensively examine and discuss how AIT can affect both the innate and the adaptive immune responses at different cell levels and propose timing-scheduled alterations induced by AIT by hypothesizing five sequential phases: after the desensitization of effector non-lymphoid cells and a transient increase of IgE (phase 1), high doses of allergen given by AIT stimulate the shift from type 2/type 3 towards type 1 response (phase 2), which is progressively potentiated by the increase of IFN-γ that promotes the chronic activation of APCs, progressively leading to the hyperexpression of Notch1L (Delta4) and the secretion of IL-12 and IL-27, which are essential to activate IL-10 gene in Th1 and ILC1 cells. As consequence, an expansion of circulating memory Th1/Tr1 cells and ILC-reg characterizes the third phase addressed to antagonize/balance the excess of type 1 response (phase 3). The progressive increase of IL-10 triggers a number of regulatory circuits sustained by innate and adaptive immune cells and favoring T-cell tolerance (phase 4), which may also be maintained for a long period after AIT interruption (phase 5). Different administration approaches of AIT have shown a similar tailoring of the immune responses and can be monitored by timely, optimized biomarkers. The clinical failure of this treatment can occur, and many genetic/epigenetic polymorphisms/mutations involving several immunological mechanisms, such as the plasticity of immune responses and the induction/maintenance of regulatory circuits, have been described. The knowledge of how AIT can shape the immune system and its responses is a key tool to develop novel AIT strategies including the engineering of allergen or their epitopes. We now have the potential to understand the precise causes of AIT failure and to establish the best biomarkers of AIT efficacy in each phase of the treatment.

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IL‐37 regulates allergic inflammation by counterbalancing pro‐inflammatory IL‐1 and IL‐33

Abstract: This is an open access article under the terms of the Creat ive Commo ns Attri butio n-NonCo mmerc ial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Cited by 32 publications

References 91 publications

Bronchial inflammation biomarker patterns link humoral immunodeficiency with bronchiectasis‐related small airway dysfunction

Bronchial inflammation biomarker patterns link humoral immunodeficiency with bronchiectasis‐related small airway dysfunction

Respiratory Symptoms, Allergies, and Environmental Exposures in Children with and without Asthma

How the Immune System Responds to Allergy Immunotherapy

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