Airway Exposure to House Dust Mite Promotes the Development of Allergy to Egg White in Mice DOI Creative Commons
Sara Benedé, Leticia Pérez‐Rodríguez, David Menchén‐Martínez

et al.

Clinical & Experimental Allergy, Journal Year: 2024, Volume and Issue: 54(10), P. 777 - 780

Published: July 15, 2024

Cases of adverse reactions to food in young children at their first known exposure have raised intriguing questions about allergy development, leading the hypothesis that sensitisation, least certain allergens such as peanut, may occur by contact through non-oral pathways like airway inhalation [1]. Interestingly, biological activity house dust mite (HDM) stimulates bystander responses other proteins, which implies respiratory present domestic dust, egg proteins could potentially lead systemic sensitisation [2]. These findings suggest possibility prior tract, facilitated adjuvant accompanying HDM components, allergies when is later ingested, a way similar described for peanuts [3, 4]. To test this hypothesis, we used murine model without exogenous adjuvants, investigate immunostimulant properties proteolytically active and inactive forms development white (EW) administered either or orally. Six-week-old female BALB/c mice received intranasally six doses HDM, (hereafter iHDM), combinations EW + iHDM, followed eight intragastric gavages with EW, before being challenged EW. Materials methods are provided open access repository OSF (https://doi.org/10.17605/OSF.IO/YCNPF). Mice its iHDM developed EW-specific IgE IgG1 antibodies, while alone did not induce antibodies specific after repeated oral administrations over 2 weeks (Figure 1a). Repeated elicit clinical signs temperature changes, but, on Day 39, jejunal concentration MCP-1 was significantly elevated had 1b), indicating mast cell activation degranulation intestinal mucosa produced towards Conversely, intranasal challenge caused anaphylaxis symptoms previously airways, particularly groups also experienced significant drops, showing both extracts following challenge. Consistently, lung homogenates exposed 1b). receiving exhibited higher levels IL-6 IL-4, level TNF-α Analyses lungs expression genes encoding tight junction revealed Cldn3 (claudin 3) Tjp1 (zonula occludens 1) were upregulated mouse combination 1c). However, epithelial alarmins, Il33 (IL-33), Il25 (IL-25) Tslp (TSLP), well Il6 (IL-6), Il17 (IL-17) Gata3 (GATA3) remained all experimental (not shown). Evaluation dendritic (DC) involved stimulation Th2 tissues Irf4 (IRF4, interferon regulatory factor 4) differentially enhanced After concanavalin A, spleen cells IL-5 IL-13, those released IL-4 culture medium 1d), conjunction promoted responses. The has been attributed degradation proteases [5, 6]. In lungs, induces production innate cytokines, which, combined co-exposed promote migration DCs lung-draining lymph nodes, IgE, ultimately triggering peanut [3]. these barrier effects partially reversible, de novo protein synthesis helps maintain junctional integrity [7]. This explains upregulation our study, would act compensatory mechanism improve function. Similarly, fact detect changes gene alarmins probably reflects time elapsed since last iHDM. addition proteolytic activity, immunity via TLR4 TLR2 signalling compounds initiate polarisation [8, 9]. Notably, increased homogenates, arises from inflammatory downstream common TLR adaptor MyD88. agreement results, Smeekens et al. [4] found plays minor role household concluding ligands activate MyD88 crucial components responsible immunomodulatory simultaneously inhaled mice. conclusion, extracts, whether inactive, Th2-driven immune response allergic manifestations. presence slightly effect, suggesting protease played modest context. Study concept design, analysis interpretation data drafting manuscript: Sara Benedé Rosina López-Fandiño. Active conduct experiments: Benedé, David Menchén-Martínez Leticia Pérez-Rodríguez. Review revision Elena Molina Obtained funding: All protocols European Legislation (directive 2010/63/EU) approved Comunidad Madrid (Ref PROEX 286.8/20). authors declare no conflicts interest. support study available request corresponding author.

Language: Английский

Immunomodulatory properties of mesenchymal stem cells: A potential therapeutic strategy for allergic rhinitis DOI Open Access
Ming Wang, Ning Zhao, Chengshuo Wang

et al.

Allergy, Journal Year: 2023, Volume and Issue: 78(6), P. 1425 - 1440

Published: March 28, 2023

Abstract Allergic rhinitis is a highly prevalent chronic inflammatory disorder of the nasal mucosa that poses significant burden on patients' health and quality life. Current therapies for allergic are unable to reinstate immune homeostasis or restricted by specific allergens. Potential therapeutic strategies urgently needed. Mesenchymal stem cells (MSCs) immune‐privileged, have strong immunomodulatory effects, can be easily isolated from various sources. Thus, MSC‐based demonstrate potential treating diseases. Recently, numerous studies investigated effects MSCs in animal models rhinitis. Here, we review mechanisms airway inflammation, especially rhinitis, highlight recent research regarding modulation cells, discuss clinical therapy

Language: Английский

Citations

19

The epithelial barrier theory: development and exacerbation of allergic and other chronic inflammatory diseases DOI Open Access
Umut Can Küçüksezer, Cevdet Özdemir, Duygu Yazıcı

et al.

Asia Pacific Allergy, Journal Year: 2023, Volume and Issue: unknown

Published: March 31, 2023

It is now longer than half a century, humans, animals, and nature of the world are under influence exposure to many newly introduced noxious substances. These exposures nowadays pushing borders be considered as causative or exacerbating factors for chronic disorders including allergic, autoimmune/inflammatory, metabolic diseases. The epithelial linings serve outermost body’s primary physical, chemical, immunological barriers against external stimuli. “epithelial barrier theory” hypothesizes that these diseases aggravated by an ongoing periepithelial inflammation triggered wide range barrier–damaging insults lead “epithelitis” release alarmins. A leaky enables microbiome’s translocation from periphery interepithelial even deeper subepithelial areas together with allergens, toxins, pollutants. Thereafter, microbial dysbiosis, characterized colonization opportunistic pathogen bacteria loss number biodiversity commensal take place. Local inflammation, impaired tissue regeneration, remodeling characterize disease. infiltration inflammatory cells affected tissues shows effort expulse invading bacteria, pollutants away deep surface, representing “expulsion response.” Cells migrate other organs foci may play roles in exacerbation various distant organs. purpose this review highlight appraise recent opinions findings on physiology its role pathogenesis view theory.

Language: Английский

Citations

18

Thymic Stromal Lymphopoietin (TSLP), Its Isoforms and the Interplay with the Epithelium in Allergy and Asthma DOI Open Access
Sylwia Smolińska, Darío Antolín‐Amérigo, Florin‐Dan Popescu

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(16), P. 12725 - 12725

Published: Aug. 12, 2023

Thymic stromal lymphopoietin (TSLP) is a pleiotropic cytokine that has emerged as critical player in the development and progression of allergy asthma. It primarily produced by epithelial cells functions potent immune system activator. TSLP acts through interaction with its receptor complex, composed (TSLPR) interleukin-7 alpha chain (IL-7Rα), activating downstream complex signalling pathways. The major isoform, known long-form (lfTSLP), upregulated airway epithelium patients allergic diseases. More research warranted to explore precise mechanisms which short-form (sfTSLP) regulates responses. Understanding dynamic interplay between dysfunctional provides insights into underlying asthma pathogenesis. Targeting represents an important therapeutic strategy, it may upstream disrupt inflammatory cascade alleviate symptoms associated inflammation.

Language: Английский

Citations

14

Airborne indoor allergen serine proteases and their contribution to sensitisation and activation of innate immunity in allergic airway disease DOI Creative Commons
Xuan Ouyang, James Reihill, Lisa Douglas

et al.

European Respiratory Review, Journal Year: 2024, Volume and Issue: 33(172), P. 230126 - 230126

Published: April 24, 2024

Common airborne allergens (pollen, animal dander and those from fungi insects) are the main triggers of type I allergic disorder in respiratory system associated with rhinitis, asthma, as well immunoglobulin E (IgE)-mediated bronchopulmonary aspergillosis. These promote IgE crosslinking, vasodilation, infiltration inflammatory cells, mucosal barrier dysfunction, extracellular matrix deposition smooth muscle spasm, which collectively cause remodelling airways. Fungus insect (house dust mite cockroaches) indoor particularly rich proteases. Indeed, more than 40 different types aeroallergen proteases, have both IgE-neutralising tissue-destructive activities, been documented Allergen Nomenclature database. Of all inhaled protease allergens, 85% classed serine activities include trypsin-like, chymotrypsin-like collagenolytic In this article, we review compare allergenicity proteolytic effect allergen proteases listed MEROPS databases highlight their contribution to sensitisation, disruption epithelial activation innate immunity airways disease. The utility small-molecule inhibitors a potential treatment strategy for disease will also be discussed.

Language: Английский

Citations

5

Polymerised mite allergoids with glutaraldehyde reduce proteolytic activity and enhance the stability of allergen mixtures: a proof of concept with grass mixtures DOI Creative Commons

José Ignacio Tudela,

Irene Soria,

Eva Abel-Fernández

et al.

Frontiers in Allergy, Journal Year: 2025, Volume and Issue: 6

Published: Feb. 25, 2025

Polysensitized patients require allergen immunotherapy (AIT) targeting multiple allergens. However, combining extracts can lead to instability and reduced efficacy particularly due the high proteolytic activity of house dust mite (HDM) While is known that glutaraldehyde cross-linking may reduce enzymatic activity, its ability stabilize multi-allergen formulations protect key allergens from degradation remains unexplored. To evaluate impact polymerization on stability immunogenicity HDM grass pollen formulations, addressing challenges in vaccines. Stability was assessed over 24 months through protein quantification antigenic assays. Proteolytic HDM-containing measured using Azocoll, peptide substrate-based Grass evaluated by SDS-PAGE, immunoblotting, ELISA Immunogenicity mice immunized with allergoids alone or combination glutaraldehyde-polymerised HDM, measuring IgG responses, splenocyte proliferation, IL-10 production. Glutaraldehyde significantly (p < 0.0001), achieving reductions 97.7%, 77.9%, 89.9% total protease cysteine serine respectively. This inhibition protected when mixed degradation, ensuring consistent content months. Mice combined polymerised showed similar responses T-cell activation, indicating no compromise immune response allergens, secretion confirming preserved regulatory responses. Polymerised address offering stable, immunogenic vaccines maintain provide a reliable treatment option for polyallergic patients.

Language: Английский

Citations

0

Thymic Stromal Lymphopoietin and Tezepelumab in Airway Diseases: From Physiological Role to Target Therapy DOI Creative Commons
Diego Bagnasco, Laura De Ferrari,

Benedetta Bondi

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(11), P. 5972 - 5972

Published: May 29, 2024

Thymic stromal lymphopoietin (TSLP), is a protein belonging to class of epithelial cytokines commonly called alarmins, which also includes IL-25 and IL-33. Functionally, TSLP key player in the immune response environmental insults, initiating number downstream inflammatory pathways. performs its role by binding high-affinity heteromeric complex composed thymic receptor (TSLPR) chain IL-7Rα. In recent years, important proinflammatory etiopathogenesis various chronic diseases such as asthma, rhinosinusitis with nasal polyposis (CRSwNP), obstructive pulmonary (COPDs), spontaneous urticaria has been studied. Although alarmins have found be mainly implicated mechanisms type 2 inflammation, studies on monoclonal antibodies against demonstrate partial efficacy even patients whose inflammation not definable T2 so-called low T2. Tezepelumab human anti-TSLP antibody that prevents TSLP-TSLPR interactions. Several clinical trials are evaluating safety disorders. this review, we will highlight major advances understanding functional TSLP, involvement Th2-related diseases, suitability target for biological therapies.

Language: Английский

Citations

4

Ingested house dust mite favors sensitization to egg white in mice independently of its proteinase activity DOI Creative Commons
Sara Benedé, Leticia Pérez‐Rodríguez, David Menchén‐Martínez

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 20, 2025

Background It is well-documented that house dust mite (HDM) exposure can cause tissue damage and activate innate immune responses. However, its role in promoting gastrointestinal sensitization allergenicity to food proteins has been relatively unexplored. Methods This study investigates the immunostimulatory effects of HDM a murine model oral egg white (EW) absence exogenous adjuvants. Additionally, we examined proteolytically inactivated form (iHDM) assess contribution protease activity adjuvant potential. Results Both iHDM enhanced allergic responses EW via route, evidenced by mast cell degranulation intestinal tract upon challenge. Notably, only induced detectable concentrations serum EW-specific IgE IgG1 antibodies. Whereas increased expression genes encoding tight junction Th2-inducing alarmins greater extent than iHDM, active proteinases were not required for activity, as preferentially promoted Th2 lymphoid tissues. Conclusions These findings suggest ingestion environmental may contribute allergy development highlight complex context-dependent nature HDM.

Language: Английский

Citations

0

Activation of the Coagulation Cascade as a Universal Danger Sign DOI Creative Commons

Э. А. Старикова,

J. T. Mammedova, Artem Rubinstein

et al.

Current Issues in Molecular Biology, Journal Year: 2025, Volume and Issue: 47(2), P. 108 - 108

Published: Feb. 9, 2025

Hemostasis is a mechanism that stops bleeding from an injured vessel, involves multiple interlinked steps, culminating in the formation of “clot” sealing damaged area. Moreover, it has long been recognized inflammation also provokes activation coagulation system. However, there increasing amount evidence revealing immune function hemostasis This review collects and analyzes results experimental studies data clinical observations confirming inflammatory hemostasis. Here, we summarize latest knowledge pathways system under influence factors. The analyzed allow us to consider components as receptors recognizing «foreign» or «self» or/and damage signals initiate reinforce affect direction adaptive response. To sum up, findings collected classify factors, such Damage-Associated Molecular Patterns break down conventional concepts

Language: Английский

Citations

0

Immunology of Nasal Polyposis and Allergic Rhinitis DOI
Sven Schneider, Julia Eckl‐Dorna

Elsevier eBooks, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

0

Allergy Treatment: A Comprehensive Review of Nanoparticle-based Allergen Immunotherapy DOI Creative Commons
Mabrouk Abo-Zaid, Reem M. Elsapagh,

Nourhan S. Sultan

et al.

Frontiers in Bioscience-Landmark, Journal Year: 2025, Volume and Issue: 30(3)

Published: March 20, 2025

Allergic disorders rising in prevalence globally, affecting a substantial proportion of individuals industrialized nations. The imbalance the immune system, characterized by elevated allergen-specific T helper 2 (Th2) cells and immunoglobulin E (IgE) antibodies, is key factor allergy development. Allergen-specific immunotherapy (AIT) only treatment capable alleviating allergic symptoms, preventing new sensitizations, reducing asthma risk rhinitis patients. Traditional AIT, however, faces challenges such as frequent administration, adverse effects, inconsistent patient outcomes. Nanoparticle-based approaches have emerged promising strategy to enhance AIT. This review explores utilization nanoparticles highlighting their ability interact with system improve therapeutic Various types nanoparticles, including polyesters, polysaccharide polymers, liposomes, protamine-based (NPs), polyanhydrides, been employed adjuvants or carriers AIT’s efficacy safety. Nanoparticles offer advantages allergen protection, improved response modulation, targeted cell delivery, reduced side effects. provides an overview current landscape nanoparticle-based immunotherapy, discussing its potential revolutionize compared traditional immunotherapy.

Language: Английский

Citations

0