Interleukins 4 and 13 in Asthma: Key Pathophysiologic Cytokines and Druggable Molecular Targets

Frontiers in Pharmacology, Journal Year: 2022, Volume and Issue: 13

Published: March 8, 2022

Interleukins (IL)-4 and -13 play a pivotal role in the pathobiology of type-2 asthma. Indeed, IL-4 is crucially involved Th2 cell differentiation, immunoglobulin (Ig) class switching eosinophil trafficking. IL-13 cooperates with promoting IgE synthesis, also induces nitric oxide (NO) production, goblet metaplasia fibroblast proliferation, as well elicits contractile responses hyperplasia airway smooth muscle cells. share common signaling pathways, activated by binding both cytokines to receptor complexes including α-subunit (IL-4Rα). Therefore, subsequent dimerization responsible for pathophysiologic effects IL-13. By selectively blocking IL-4Rα, fully human IgG4 monoclonal antibody dupilumab behaves dual antagonist Through this mechanism action, exerts effective therapeutic actions inflammation, thus decreasing asthma exacerbations, FeNO (fractional exhaled NO) levels, intake oral corticosteroids (OCS). In addition being approved add-on biological therapy severe asthma, has been licensed treatment nasal polyposis atopic dermatitis.

Language: Английский

---

Mucus Structure, Viscoelastic Properties, and Composition in Chronic Respiratory Diseases

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(3), P. 1933 - 1933

Published: Feb. 5, 2024

The respiratory mucus, a viscoelastic gel, effectuates primary line of the airway defense when operated by mucociliary clearance. In chronic diseases (CRDs), such as asthma, obstructive pulmonary disease (COPD), and cystic fibrosis (CF), mucus is overproduced its solid content augments, changing structure properties determining derangement essential mechanisms against opportunistic microbial (virus bacteria) pathogens. This ensues in damaging airways, leading to vicious cycle obstruction infection responsible for harsh clinical evolution these CRDs. Here, we review features normal pathological (i.e., sputum CF, COPD, asthma), i.e., mucin content, (mesh size), micro/macro-rheology, pH, osmotic pressure, ending with awareness that biomarkers (mucins, inflammatory proteins peptides, metabolites) might serve indicate acute exacerbation response therapies. There are some indications old novel treatments may change structure, properties, biomarker sputum; however, wealth work still needed embrace measures correlates severity association (or even substitutes of) functional tests.

Language: Английский

---

Climate change, airborne allergens, and three translational mitigation approaches

EBioMedicine, Journal Year: 2023, Volume and Issue: 93, P. 104478 - 104478

Published: Feb. 17, 2023

Language: Английский

---

Pathobiology of Type 2 Inflammation in Asthma and Nasal Polyposis

Journal of Clinical Medicine, Journal Year: 2023, Volume and Issue: 12(10), P. 3371 - 3371

Published: May 9, 2023

Asthma and nasal polyposis often coexist are frequently intertwined by tight pathogenic links, mainly consisting of the cellular molecular pathways underpinning type 2 airway inflammation. The latter is characterized a structural functional impairment epithelial barrier, associated with eosinophilic infiltration both lower upper airways, which can be driven either allergic or non-allergic mechanisms. Type inflammatory changes predominantly due to biological actions exerted interleukins 4 (IL-4), 13 (IL-13), 5 (IL-5), produced T helper (Th2) lymphocytes group innate lymphoid cells (ILC2). In addition above cytokines, other proinflammatory mediators involved in pathobiology asthma include prostaglandin D2 cysteinyl leukotrienes. Within this context ‘united diseases’, encompasses several nosological entities such as chronic rhinosinusitis polyps (CRSwNP) aspirin-exacerbated respiratory disease (AERD). Because common origins polyposis, it not surprising that more severe forms these disorders successfully treated same biologic drugs, targeting many components (IgE, IL-5 its receptor, IL-4/IL-13 receptors) trait.

Language: Английский

---

Co-exposure to polystyrene microplastics and di-(2-ethylhexyl) phthalate aggravates allergic asthma through the TRPA1-p38 MAPK pathway

Toxicology Letters, Journal Year: 2023, Volume and Issue: 384, P. 73 - 85

Published: July 26, 2023

Language: Английский

---

Immunological factors, important players in the development of asthma

BMC Immunology, Journal Year: 2024, Volume and Issue: 25(1)

Published: July 26, 2024

Abstract Asthma is a heterogeneous disease, and its development the result of combination factors, including genetic environmental immune dysfunction other factors. Its specific mechanism has not yet been fully investigated. With improvement disease models, research on pathogenesis asthma made great progress. Immunological disorders play an important role in asthma. Previously, we thought that was mainly caused by imbalance between Th1 Th2 responses, but this theory cannot explain Recent studies have shown T-cell subsets such as cells, Th17 Tregs their cytokines contribute to through different mechanisms. For purpose present study, classified into distinct phenotypes based airway inflammatory eosinophilic asthma, characterized predominant eosinophil aggregates, neutrophilic neutrophil aggregates. This paper will examine mechanisms underlying types utilize data from animal models clinical targeting pathways inform more precise treatments for condition.

Language: Английский

---

Fecal Microbiota Transplantation Alleviates Allergic Rhinitis via CD4+ T Cell Modulation Through Gut Microbiota Restoration

Inflammation, Journal Year: 2024, Volume and Issue: 47(4), P. 1278 - 1297

Published: Jan. 31, 2024

Language: Английский

---

Exploring the immunopathology of type 2 inflammatory airway diseases

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: April 12, 2024

Significant advancements have been achieved in understanding the roles of different immune cells, as well cytokines and chemokines, pathogenesis eosinophilic airway conditions. This review examines Chronic Rhinosinusitis with Nasal Polyps (CRSwNP), marked by complex dysregulation, major contributions from type 2 inflammation dysfunctional epithelium. The presence eosinophils role T-cell subsets, particularly an imbalance between Treg Th17 are crucial to disease’s pathogenesis. also investigates asthma, a unique asthma subtype. It is characterized high eosinophil levels, playing pivotal triggering inflammation. response involves Th2 eosinophils, IgE, among others, all activated genetic environmental factors. intricate interplay these elements, innate lymphoid cells results hyper-responsiveness, contributing asthma. Another scope this Eosinophilic Granulomatosis Polyangiitis (EGPA); inflammatory disease that commonly affects respiratory tract small medium-sized blood vessels. elevated levels tissues. activation adaptive responses antigens leading T B cell stimulation, which causes tissue vessel damage. On other hand, Allergic Bronchopulmonary Aspergillosis (ABPA) hypersensitive occurs when airways become colonized aspergillus fungus, involving responses, production IgE antibodies, action bronchial subsequent lung analysis scrutinizes how imbalanced system contributes diseases. derived assessment can steer researchers toward designing new potential therapeutic targets for efficient control disorders.

Language: Английский

---

Migrasomes derived from human umbilical cord mesenchymal stem cells: a new therapeutic agent for ovalbumin-induced asthma in mice

Stem Cell Research & Therapy, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 26, 2025

Asthma is a prevalent respiratory disease, and its management remains largely unsatisfactory. Mesenchymal stem cells (MSCs) have been demonstrated to be efficacious in reducing airway inflammation experimental allergic diseases, representing potential alternative treatment for asthma. Migrasomes are recently identified extracellular vesicles (EVs) generated migrating facilitate intercellular communication. The objective of this study was investigate the therapeutic effects migrasomes obtained from MSC model produced by human umbilical cord MSCs (hUCMSCs) were isolated sequential centrifugation. Characterization hUCMSC-derived carried out transmission electron microscopy western blot analysis. on ovalbumin (OVA)-induced asthmatic mice evaluated hematoxylin-eosin (HE) periodic-acid schiff (PAS) staining, their mechanism further testified immunofluorescent real-time PCR flow cytometry. Here, we showed that inhibition migrasomes' production dramatically impaired anti-inflammatory hUCMSCs OVA animals, as evidenced notable increase both infiltration inflammatory number epithelial goblet cells. We successfully hUCMSC-migrasomes, which morphologically intact positive specific markers. administration hUCMSC-migrasomes observed significantly ameliorate symptoms mucus mice. Additionally, expression Th2 cytokines (IL-4, IL-5 IL-13) found reduced, while activation dendritic (DCs) inhibited. HUCMSC-migrasomes could possibly delivered lung region after injection, able taken DCs vivo vitro. Notably, vitro, migraosmes decreased capacity BMDCs stimulate OVA-specific Th2-cell responses. More importantly, adoptive transfer hUCMSC-migrasomes-treated sufficient protect inflammation. In addition, inhibited receptor advanced glycation end-products (RAGE) signal OVA-treated vitro asthma vivo. Our results provided first evidence possess properties OVA-induced mice, may provide novel "MSC-cell free" agent

Language: Английский

---

Pharmaceutical targeting Th2-mediated immunity enhances immunotherapy response in breast cancer

Journal of Translational Medicine, Journal Year: 2022, Volume and Issue: 20(1)

Published: Dec. 23, 2022

Abstract Background Breast cancer is a complex disease with highly immunosuppressive tumor microenvironment, and has limited clinical response to immune checkpoint blockade (ICB) therapy. T-helper 2 (Th2) cells, an important component of the microenvironment (TME), play essential role in regulation immunity. However, deep relationship between Th2-mediated immunity evasion breast remains enigmatic. Methods Here, we first used bioinformatics analysis explore correlation Th2 infiltration landscape cancer. Suplatast tosilate (IPD-1151 T, IPD), inhibitor function, was then employed investigate biological effects on growth immunocompetent murine models. The analyzed by flow cytometry, mass immunofluorescence staining. Furthermore, examined efficacy IPD combination ICB treatment evaluating TME, mice survival. Results Our suggested that higher cells indicates In three models (EO771, 4T1 EMT6), significantly inhibited IL-4 secretion promoted Th1 switching, remodeled growth. Remarkably, CD8 + T cell cytotoxic activity lymphocyte (CTL) tissues were evidently enhanced after treatment. increased effector CD4 decreased myeloid-derived suppressor M2-like macrophages also demonstrated IPD-treated tumors. Importantly, found reinforced therapeutic without increasing potential adverse effects. Conclusions findings demonstrate pharmaceutical inhibition function improves via remodeling which illustrates promising combinatorial immunotherapy.

Language: Английский

---