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Allergic Diseases and Metabolism
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Allergic Diseases and Metabolism

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Endocrinology and Metabolism".

Deadline for manuscript submissions: closed (30 September 2023) | Viewed by 21566

Special Issue Editors

Dr. Sylwia Smolińska

E-Mail Website
Guest Editor
Department of Clinical Immunology, Faculty of Medicine, Wroclaw Medical University, Parkowa 34, 51-616 Wroclaw, Poland
Interests: microbiome; asthma; allergies; intestinal tract; exposome
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Marek Jutel

E-Mail Website
Guest Editor
Department of Clinical Immunology, Wroclaw Medical University, 50-368 Wroclaw, Poland
Interests: clinical immunology; allergies

Special Issue Information

Dear Colleagues,

Inflammatory immune responses against harmless environmental allergens arise from complex interactions between different types of immune cells. Activated immune cells undergo extensive changes in phenotype to fulfill their effector functions. Activation, differentiation, proliferation, migration, and mounting of effector responses require metabolic reprogramming. Many studies already have shown that the innate key cell types in allergic inflammation change their metabolic phenotype during activation. There is increasing evidence that the metabolic status of T cells and macrophages is associated with severe phenotypes of chronic inflammation, including allergic inflammation. Immune cells under specific microenvironment changes display different metabolic responses. This metabolic reprogramming can be initiated not only by nutrient conditions but also by disease-related molecules, such as inflammatory molecules, pathogens, or allergens. While the metabolic changes associated with activation of dendritic cells, macrophages, and T cells are extensively studied, data about the metabolic phenotypes of the other cell types critically involved in allergic responses (epithelial cells, eosinophils, basophils, mast cells, and ILC2s) are rather limited. Therefore, immune metabolism is of relevance in allergic diseases and its connection to immune cell effector function needs to be considered to better understand induction and maintenance of allergic responses. Improving our understanding of allergic disease pathology enable new treatment targets and strategies.This link between energy metabolism and inflammation can be studied employing animal, human or cellular models. Analytical approaches rank from classic immunological studies to integrated analysis of metabolomics, transcriptomics, and proteomics.               

The scope of this topic covers the basics and advances of cellular energy metabolism and its connection to immune cell function, especially focuses on the metabolic changes associated with activation of epithelial cells, eosinophils, basophils, mast cells, dendritic cells and macrophages, as well as ILC2s in allergic diseases and asthma. Taken together, studies of metabolism have a great potential to open doors to a new class of therapeutic strategies, better characterization of disease endotypes, as well as enable a systems biology approach to mechanisms of allergic disease. Feel welcome to join the project!

Dr. Sylwia Smolinska
Prof. Dr. Marek Jutel
Guest Editors

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Keywords

  • immune cells metabolism
  • allergies
  • metabolic reprogramming
  • energy metabolism
  • metabolic changes

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Published Papers (5 papers)

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Research

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11 pages, 451 KiB  
Article
Clinical Application of In Vitro Tests for COVID-19 Vaccine Delayed Hypersensitivity Diagnostics
by Jan Romantowski, Aleksandra Górska, Maciej Zieliński, Piotr Trzonkowski, Karolina Rucka and Marek Niedoszytko
Int. J. Mol. Sci. 2023, 24(17), 13296; https://doi.org/10.3390/ijms241713296 - 27 Aug 2023
Cited by 1 | Viewed by 1703
Abstract
Drug hypersensitivity reactions can be classified as immediate or delayed. While diagnostic options for immediate reactions are well developed and standardized, delayed reactions (in many cases type IV according to Gell and Coombs) are a challenge for allergy work-up. In recent years, some [...] Read more.
Drug hypersensitivity reactions can be classified as immediate or delayed. While diagnostic options for immediate reactions are well developed and standardized, delayed reactions (in many cases type IV according to Gell and Coombs) are a challenge for allergy work-up. In recent years, some in vitro markers have been proposed and used for delayed reactions, such as contact dermatitis. Primary strategy: Avoidance is difficult to achieve, especially for COVID-19 vaccinations, when immunity against infection is extremely important. The aim of our study was to evaluate the application of in vitro delayed hypersensitivity tests in COVID-19 vaccines. Seven patients with a positive history of severe delayed drug allergy were enrolled. Vein blood was collected to stimulate cells with the tested vaccines (Comirnaty, Janssen, Spikevax) and excipients with the assessment of CD40L, CD69, IL-2, IL-4, IL-6, IL-10, IFNgamma, TNFalfa, and intracellular markers: granulysin and INFgamma. In addition, basophile activation tests, patch tests, skin prick tests, and intradermal tests were performed with the tested vaccine. Finally, the decision was made to either administer a vaccine or resign. Two out of seven patients were considered positive for drug hypersensitivity in the in vitro test according to the high vaccine stimulation index measured with CD69 (6.91 and 12.18) and CD40L (5.38 and 15.91). All patch tests, BATs, and skin tests were negative. Serum interleukin measurements were inconclusive as the impact of the vaccine itself on the immunity system was high. Intracellular markers gave uncertain results due to the lack of stimulation on the positive control. CD69 and CD40L could be reliable in vitro markers for delayed hypersensitivity to COVID-19 vaccines. Patch tests, skin tests, BATs, and serum interleukins did not confirm their usefulness in our study. Full article
(This article belongs to the Special Issue Allergic Diseases and Metabolism)
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16 pages, 5139 KiB  
Article
Fallopia japonica Root Extract Ameliorates Ovalbumin-Induced Airway Inflammation in a CARAS Mouse Model by Modulating the IL-33/TSLP/NF-κB Signaling Pathway
by Juan Jin, Yan Jing Fan, Thi Van Nguyen, Zhen Nan Yu, Chang Ho Song, So-Yong Lee, Hee Soon Shin and Ok Hee Chai
Int. J. Mol. Sci. 2023, 24(15), 12514; https://doi.org/10.3390/ijms241512514 - 7 Aug 2023
Cited by 15 | Viewed by 2571
Abstract
Fallopia japonica (Asian knotweed) is a medicinal herb traditionally used to treat inflammation, among other conditions. However, the effects of F. japonica root extract (FJE) on airway inflammation associated with combined allergic rhinitis and asthma (CARAS) and the related mechanisms have not been [...] Read more.
Fallopia japonica (Asian knotweed) is a medicinal herb traditionally used to treat inflammation, among other conditions. However, the effects of F. japonica root extract (FJE) on airway inflammation associated with combined allergic rhinitis and asthma (CARAS) and the related mechanisms have not been investigated. This study examined the effect of FJE against CARAS in an ovalbumin (OVA)-induced CARAS mouse model. Six-week-old male BALB/c mice were randomly segregated into six groups. Mice were sensitized intraperitoneally with OVA on days 1, 8, and 15, and administered saline, Dexamethasone (1.5 mg/kg), or FJE (50, 100, or 200 mg/kg) once a day for 16 days. Nasal symptoms, inflammatory cells, OVA-specific immunoglobulins, cytokine production, mast cell activation, and nasal histopathology were assessed. Administration of FJE down-regulated OVA-specific IgE and up-regulated OVA-specific IgG2a in serum. FJE reduced the production of T helper (Th) type 2 cytokines, and the Th1 cytokine levels were enhanced in nasal and bronchoalveolar lavage fluid. Moreover, FJE positively regulated allergic responses by reducing the accumulation of inflammatory cells, improving nasal and lung histopathological characteristics, and inhibiting inflammation-associated cytokines. FJE positively modulated the IL-33/TSLP/NF-B signaling pathway, which is involved in regulating inflammatory cells, immunoglobulin levels, and pro-inflammatory cytokines at the molecular level. Full article
(This article belongs to the Special Issue Allergic Diseases and Metabolism)
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17 pages, 1724 KiB  
Article
Relationship between IgE Levels Specific for Ragweed Pollen Extract, Amb a 1 and Cross-Reactive Allergen Molecules
by Lauriana-Eunice Zbîrcea, Maria-Roxana Buzan, Manuela Grijincu, Elijahu Babaev, Frank Stolz, Rudolf Valenta, Virgil Păunescu, Carmen Panaitescu and Kuan-Wei Chen
Int. J. Mol. Sci. 2023, 24(4), 4040; https://doi.org/10.3390/ijms24044040 - 17 Feb 2023
Cited by 13 | Viewed by 4832
Abstract
Ragweed (Ambrosia artemisiifolia) pollen is a major endemic allergen source responsible for severe allergic manifestations in IgE-sensitized allergic patients. It contains the major allergen Amb a 1 and cross-reactive allergen molecules, such as the cytoskeletal protein profilin, Amb a 8 and [...] Read more.
Ragweed (Ambrosia artemisiifolia) pollen is a major endemic allergen source responsible for severe allergic manifestations in IgE-sensitized allergic patients. It contains the major allergen Amb a 1 and cross-reactive allergen molecules, such as the cytoskeletal protein profilin, Amb a 8 and calcium-binding allergens Amb a 9 and Amb a 10. To assess the importance of Amb a 1, profilin and calcium-binding allergen, the IgE reactivity profiles of clinically well-characterized 150 ragweed pollen-allergic patients were analysed regarding specific IgE levels for Amb a 1 and cross-reactive allergen molecules by quantitative ImmunoCAP measurements, IgE ELISA and by basophil activation experiments. By quantifying allergen-specific IgE levels we found that Amb a 1-specific IgE levels accounted for more than 50% of ragweed pollen-specific IgE in the majority of ragweed pollen-allergic patients. However, approximately 20% of patients were sensitized to profilin and the calcium-binding allergens, Amb a 9 and Amb a 10, respectively. As shown by IgE inhibition experiments, Amb a 8 showed extensive cross-reactivity with profilins from birch (Bet v 2), timothy grass (Phl p 12) and mugwort pollen (Art v 4) and was identified as a highly allergenic molecule by basophil activation testing. Our study indicates that molecular diagnosis performed by the quantification of specific IgE to Amb a 1, Amb a 8, Amb a 9 and Amb a 10 is useful to diagnose genuine sensitization to ragweed pollen and to identify patients who are sensitized to highly cross-reactive allergen molecules present in pollen from unrelated plants, in order to enable precision medicine-based approaches for the treatment and prevention of pollen allergy in areas with complex pollen sensitization. Full article
(This article belongs to the Special Issue Allergic Diseases and Metabolism)
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Review

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19 pages, 1490 KiB  
Review
Thymic Stromal Lymphopoietin (TSLP), Its Isoforms and the Interplay with the Epithelium in Allergy and Asthma
by Sylwia Smolinska, Darío Antolín-Amérigo, Florin-Dan Popescu and Marek Jutel
Int. J. Mol. Sci. 2023, 24(16), 12725; https://doi.org/10.3390/ijms241612725 - 12 Aug 2023
Cited by 14 | Viewed by 6363
Abstract
Thymic stromal lymphopoietin (TSLP) is a pleiotropic cytokine that has emerged as a critical player in the development and progression of allergy and asthma. It is primarily produced by epithelial cells and functions as a potent immune system activator. TSLP acts through interaction [...] Read more.
Thymic stromal lymphopoietin (TSLP) is a pleiotropic cytokine that has emerged as a critical player in the development and progression of allergy and asthma. It is primarily produced by epithelial cells and functions as a potent immune system activator. TSLP acts through interaction with its receptor complex, composed of the TSLP receptor (TSLPR) and interleukin-7 receptor alpha chain (IL-7Rα), activating downstream complex signalling pathways. The TSLP major isoform, known as long-form TSLP (lfTSLP), is upregulated in the airway epithelium of patients with allergic diseases. More research is warranted to explore the precise mechanisms by which short-form TSLP (sfTSLP) regulates immune responses. Understanding the dynamic interplay between TSLP and the dysfunctional epithelium provides insights into the mechanisms underlying allergy and asthma pathogenesis. Targeting TSLP represents an important therapeutic strategy, as it may upstream disrupt the inflammatory cascade and alleviate symptoms associated with allergic inflammation. Full article
(This article belongs to the Special Issue Allergic Diseases and Metabolism)
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15 pages, 1382 KiB  
Review
Bradykinin Metabolism and Drug-Induced Angioedema
by Sylwia Smolinska, Darío Antolín-Amérigo and Florin-Dan Popescu
Int. J. Mol. Sci. 2023, 24(14), 11649; https://doi.org/10.3390/ijms241411649 - 19 Jul 2023
Cited by 16 | Viewed by 5022
Abstract
Bradykinin (BK) metabolism and its receptors play a central role in drug-induced angioedema (AE) without urticaria through increased vascular permeability. Many cardiovascular and diabetic drugs may cause BK-mediated AE. Angiotensin-converting enzyme inhibitors (ACEIs) and neprilysin inhibitors impair BK catabolism. Dipeptidyl peptidase-IV (DPP-IV) inhibitors [...] Read more.
Bradykinin (BK) metabolism and its receptors play a central role in drug-induced angioedema (AE) without urticaria through increased vascular permeability. Many cardiovascular and diabetic drugs may cause BK-mediated AE. Angiotensin-converting enzyme inhibitors (ACEIs) and neprilysin inhibitors impair BK catabolism. Dipeptidyl peptidase-IV (DPP-IV) inhibitors reduce the breakdown of BK and substance P (SP). Moreover, angiotensin receptor blockers, thrombolytic agents, and statins may also induce BK-mediated AE. Understanding pathophysiological mechanisms is crucial for preventing and treating drug-induced AE. Full article
(This article belongs to the Special Issue Allergic Diseases and Metabolism)
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