Microbial Dysbiosis Tunes the Immune Response Towards Allergic Disease Outcomes

Clinical Reviews in Allergy & Immunology, Journal Year: 2022, Volume and Issue: 65(1), P. 43 - 71

Published: June 1, 2022

Abstract The hygiene hypothesis has been popularized as an explanation for the rapid increase in allergic disease observed over past 50 years. Subsequent epidemiological studies have described protective effects that utero and early life exposures to environment high microbial diversity conferring benefits against development of diseases. advancement next generation sequencing technology allowed analysis diverse nature communities present barrier organs a determination their role induction disease. Here, we discuss recent literature describing how colonization during by microbiota influences adaptive immune system. In parallel, mechanistic delivered insight into pathogenesis disease, demonstrating comparative T regulatory (Treg) cells, with inflammatory helper 2 (Th2) cells tolerance or response. More recently, significant our understanding interactions between system microbially derived factors play central emerged. Providing deeper symbiotic relationship microbiome system, which explains key observations made hypothesis. By studying perturbations drive dysbiosis can cause stand benefit delineating versus pathogenic aspects human companions, allowing us better harness use agents design novel prophylactic therapeutic strategies.

Language: Английский

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Immunomodulatory properties of mesenchymal stem cells: A potential therapeutic strategy for allergic rhinitis

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

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Epithelial Barrier Theory: The Role of Exposome, Microbiome, and Barrier Function in Allergic Diseases

Allergy Asthma and Immunology Research, Journal Year: 2023, Volume and Issue: 15(6), P. 705 - 705

Published: Jan. 1, 2023

Allergic diseases are a major public health problem with increasing prevalence.These immune-mediated characterized by defective epithelial barriers, which explained the barrier theory and continuously emerging evidence.Environmental exposures (exposome) including global warming, changes loss of biodiversity, pollution, pathogens, allergens mites, laundry dishwasher detergents, surfactants, shampoos, body cleaners household cleaners, microplastics, nanoparticles, toothpaste, enzymes emulsifiers in processed foods, dietary habits responsible for mucosal skin disruption.Exposure to barrier-damaging agents causes cell injury damage, colonization opportunistic commensal bacteria, decreased microbiota diversity, bacterial translocation, allergic sensitization, inflammation periepithelial area.Here, we review scientific evidence on environmental components that impact barriers microbiome composition their influence asthma diseases.We also discuss historical overview evolution hygiene hypothesis theoretical evidence.

Language: Английский

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A non-invasive strategy for suppressing asthmatic airway inflammation and remodeling: Inhalation of nebulized hypoxic hUCMSC-derived extracellular vesicles

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: April 5, 2023

Mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) are extremely promising nanoscale cell-free therapeutic agents. We previously identified that intravenous administration (IV) of human umbilical cord MSC-EVs (hUCMSC-EVs), especially hypoxic hUCMSC-EVs (Hypo-EVs), could suppress allergic airway inflammation and remodeling. Here, we further investigated the effects Hypo-EVs by atomizing inhalation (INH), which is a non-invasive efficient drug delivery method for lung diseases. found nebulized produced atomization system (medical/household air compressor nebulizer) maintained excellent structural integrity. Nebulized Dir-labeled inhaled mice were mainly restricted to lungs. INH significantly reduced inflammatory infiltration, decreased levels IL-4, IL-5 IL-13 in bronchoalveolar lavage fluid (BALF), declined content OVA-specific IgE serum, attenuated goblet cell metaplasia, expressions subepithelial collagen-1 α-smooth muscle actin (α-SMA). Notably, Hypo-EV was generally more potent than IV suppressing α-SMA expressions. RNA sequencing revealed various biological processes, such as adhesion, innate immune response, B activation, space, associated with activity against asthma mice. In addition, load exogenous miR-146a-5p (miR-146a-5p-EVs). Furthermore, miR-146a-5p-EVs resulted increased expression mostly lungs, offered greater protection OVA-induced increase inflammation, collagen accumulation myofibroblast compared Hypo-EVs. Overall, effectively remodeling, potentially creating route use treatment.

Language: Английский

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Single-cell analysis reveals alterations in cellular composition and cell-cell communication associated with airway inflammation and remodeling in asthma

Respiratory Research, Journal Year: 2024, Volume and Issue: 25(1)

Published: Feb. 5, 2024

Asthma is a heterogeneous disease characterized by airway inflammation and remodeling, whose pathogenetic complexity was associated with abnormal responses of various cell types in the lung. The specific interactions between immune stromal cells, crucial for asthma pathogenesis, remain unclear. This study aims to determine key their pathological mechanisms through single-cell RNA sequencing (scRNA-seq). A 16-week mouse model house dust mite (HDM) induced (n = 3) controls were profiled scRNA-seq. cellular composition gene expression profiles assessed bioinformatic analyses, including enrichment analysis, trajectory Gene Set Enrichment Analysis. Cell-cell communication analysis employed investigate ligand-receptor interactions. results coupled remodeling hyperresponsiveness. Single-cell revealed notable changes compositions heterogeneities remodeling. GdT17 cells identified be primary source IL-17, related inflammatory exacerbation, while subpopulation alveolar macrophages exhibited numerous significantly up-regulated genes involved multiple pathways neutrophil activities asthma. distinct fibroblast subpopulation, marked elevated levels contractile regulators, observed increased smooth muscle layer immunofluorescence analysis. Asthmatic stromal-immune strengthened, particularly involving interacting fibroblasts. CXCL12/CXCR4 signaling remarkedly asthma, predominantly bridging interaction fibroblasts populations. Fibroblasts could jointly interact subpopulations via CCL8/CCR2 signaling. In particular, fibroblast-macrophage circuits played role development IL1B paracrine Our established that recapitulated features ScRNA-seq landscape, highlighting populations pathogenesis. contributing findings emphasized significance cell-cell possible causality providing valuable hints therapeutic strategies

Language: Английский

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Role of Macrophages in Air Pollution Exposure Related Asthma

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(20), P. 12337 - 12337

Published: Oct. 15, 2022

Asthma is a chronic inflammatory airway disease characterized by variable airflow obstruction, bronchial hyper-responsiveness, and inflammation. The inflammation of the mediated many cell types, cytokines, chemokines, mediators. Research suggests that exposure to air pollution has negative impact on asthma outcomes in adult pediatric populations. Air one greatest environmental risks health, it impacts lungs’ innate adaptive defense systems. A major pollutant particulate matter (PM), complex component composed elemental carbon heavy metals. According WHO, 99% people live where quality levels are lower than WHO guidelines. This effect crucial health issue worldwide. Macrophages essential recognizing processing any inhaled foreign material, such as PM. Alveolar macrophages predominant types process remove PM secreting proinflammatory mediators from lung. review focuses their role orchestrating responses induced pollutants asthma.

Language: Английский

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Role of Respiratory Epithelial Cells in Allergic Diseases

Cells, Journal Year: 2022, Volume and Issue: 11(9), P. 1387 - 1387

Published: April 20, 2022

The airway epithelium provides the first line of defense to surrounding environment. However, dysfunctions this physical barrier are frequently observed in allergic diseases, which tightly connected with pro- or anti-inflammatory processes. When epithelial cells confronted allergens pathogens, specific response mechanisms set motion, homeostasis, lead elimination invaders and leave permanent traces on respiratory epithelium. can also cause damage sensitized organism, be ascribed excessive immune reactions. tight interaction upper lower airways local systemic an imprint that may mirror pathophysiology. effector T cells, along macrophages, play important role response, as reflected gene expression profiles (transcriptomes) well secretory pattern (secretomes). Further, storage information from past exposures memories within discrete cell types allow a tissue inform fundamentally alter its future responses. Recently, several lines evidence have highlighted contributions myeloid lymphoid stromal mast emerging concepts inflammatory memory trained immunity.

Language: Английский

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Emerging Insights into the Impact of Air Pollution on Immune-Mediated Asthma Pathogenesis

Current Allergy and Asthma Reports, Journal Year: 2022, Volume and Issue: 22(7), P. 77 - 92

Published: April 8, 2022

Language: Английский

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Tryptase in Acute Appendicitis: Unveiling Allergic Connections through Compelling Evidence

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(3), P. 1645 - 1645

Published: Jan. 29, 2024

The aetiology of acute appendicitis (AA), the most frequent abdominal surgical emergency, is still unclarified. Recent epidemiologic, clinical and laboratorial data point to an allergic component in pathophysiology AA. Mastocytes participate Th2 immune response, releasing inflammatory mediators from their granules upon stimulation by IgE-specific antigens. Among well-known are histamine, serotonin tryptase, which responsible for manifestations allergies. We conducted a prospective single-centre study measure histamine (commercial ELISA kit) tryptase (ImmunoCAP System) concentrations appendicular lavage fluid (ALF) serum. Consecutive patients presenting emergency department with diagnosis AA were enrolled: 22 phlegmonous 24 gangrenous control group was composed 14 referred colectomy colon malignancy. Appendectomy performed during colectomy. Tryptase levels strikingly different between histological groups, both ALF serum (p < 0.001); higher than levels. 109 times (APA) (796.8 (194.1-980.5) pg/mL) 114 (AGA) (837.4 (272.6-1075.1) (7.3 (4.5-10.3) pg/mL. For AA, discriminative power concentration good (AUC = 0.825), but weak 0.559) differential APA AGA. involved presentations appendicitis, no significant differences found. No found groups. Due short half-lives, these might have elapsed time samples collected. In future research, determinations should be made immediately after appendectomy. Our findings confirm hypersensitivity type I reaction as event occurring pathogenesis AA: among when compared group, line response supports concept presence appendicitis. results, if confirmed, may implications treatment

Language: Английский

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Novel Biological Therapies for Severe Asthma Endotypes

Biomedicines, Journal Year: 2022, Volume and Issue: 10(5), P. 1064 - 1064

Published: May 4, 2022

Severe asthma comprises several heterogeneous phenotypes, underpinned by complex pathomechanisms known as endotypes. The latter are driven intercellular networks mediated molecular components which can be targeted specific monoclonal antibodies. With regard to the biological treatments of either allergic or non-allergic eosinophilic type 2 asthma, currently available antibodies directed against immunoglobulins E (IgE), interleukin-5 (IL-5) and its receptor, receptors interleukins-4 (IL-4) 13 (IL-13), well thymic stromal lymphopoietin (TSLP) other alarmins. Among these therapeutic strategies, best choice should made according phenotypic/endotypic features each patient with severe who thus respond significant clinical functional improvements. Conversely, very poor options so far characterize experimental pipelines referring perspective management non-type thereby needs focus future thorough research.

Language: Английский

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