The Role of Natural Killer Cells in Autoimmune Diseases

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12

Published: Feb. 25, 2021

Natural killer (NK) cells, the large granular lymphocytes differentiated from common lymphoid progenitors, were discovered in early 1970's. They are members of innate immunity and initially defined by their strong cytotoxicity against virus-infected cells important effector functions anti-tumoral immune responses. Nowadays, NK classified among recently cell subsets have capacity to influence both adaptive Therefore, they can be considered as that stands between arms immunity. don't express T or B receptors recognized absence CD3. There two major subgroups according differential expression CD16 CD56. While

Language: Английский

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Allergen Immunotherapy: Current and Future Trends

Cells, Journal Year: 2022, Volume and Issue: 11(2), P. 212 - 212

Published: Jan. 8, 2022

Allergen immunotherapy (AIT) is the sole disease-modifying treatment for allergic rhinitis; it prevents rhinitis from progressing to asthma and lowers medication use. AIT against mites, insect venom, certain kinds of pollen effective. The mechanism action based on inducing immunological tolerance characterized by increased IL-10, TGF-β, IgG4 levels Treg cell counts. However, requires prolonged schemes administration sometimes associated with adverse reactions. Over last decade, novel forms have been developed, focused better allergen identification, structural modifications preserve epitopes B or T cells, post-traductional alteration through chemical processes, addition adjuvants. These modified allergens induce clinical-immunological effects similar those mentioned above, increasing other related but fewer side effects. Clinical studies shown that molecular efficient in treating grass birch allergies. This article reviews possibility a new improve illness.

Language: Английский

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Dupilumab: A Review of Present Indications and Off-Label Uses

Journal of Investigational Allergology and Clinical Immunology, Journal Year: 2021, Volume and Issue: 32(2), P. 97 - 115

Published: March 4, 2021

Recent advances in our understanding of T2 inflammation have revealed more diseases which is involved. Dupilumab a recently developed monoclonal antibody that blocks signaling IL-4 and IL-13, both are crucial cytokines the response. New possible indications increasingly explored include skin diseases, such as prurigo nodularis, nummular eczema, allergic contact dermatitis, chronic hand spontaneous urticaria, bullous pemphigoid, alopecia areata, Netherton syndrome, well respiratory bronchopulmonary aspergillosis, eosinophilic pneumonia, rhinitis. In addition, gastrointestinal disorders, particularly esophagitis, food allergy, also research fields interest. Here, we review published data clinical trials examining use dupilumab these disorders.

Language: Английский

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Dendritic Cells: Critical Regulators of Allergic Asthma

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(21), P. 7930 - 7930

Published: Oct. 26, 2020

Allergic asthma is a chronic inflammatory disease of the airways characterized by airway hyperresponsiveness (AHR), inflammation, and excessive T helper (Th) type 2 immune responses against harmless airborne allergens. Dendritic cells (DCs) represent most potent antigen-presenting system that act as bridge between innate adaptive immunity. Pertinent to allergic asthma, distinct DC subsets are known play central role in initiating maintaining allergen driven Th2 airways. Nevertheless, seminal studies have demonstrated DCs can also restrain asthmatic thus contribute resolution inflammation maintenance pulmonary tolerance. Notably, transfer tolerogenic vivo suppresses protects or even reverses established inflammation. Thus, identification novel possess immunoregulatory properties efficiently control aberrant critical for re-establishment tolerance amelioration phenotype.

Language: Английский

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Allergen Immunotherapy Enhances Airway Epithelial Antiviral Immunity in Patients with Allergic Asthma (VITAL Study): A Double-Blind Randomized Controlled Trial

American Journal of Respiratory and Critical Care Medicine, Journal Year: 2023, Volume and Issue: 207(9), P. 1161 - 1170

Published: Jan. 26, 2023

Rationale: Allergic asthma is linked to impaired bronchial epithelial secretion of IFNs, which may be causally the increased risk viral exacerbations. We have previously shown that allergen immunotherapy (AIT) effectively reduces exacerbations and prevents respiratory infections requiring antibiotics; however, whether AIT alters antiviral immunity still unknown. Objectives: To investigate effect house dust mite sublingual (HDM-SLIT) on inflammatory responses in patients with allergic asthma. Methods: In this double-blind, randomized controlled trial (VITAL [The Effect Allergen Immunotherapy Anti-viral Immunity Patients Asthma]), adult HDM received HDM-SLIT 12-SQ or placebo for 24 weeks. Bronchoscopy was performed at baseline Week 24, included sampling human cells. Human cells were cultured stimulated mimic polyinosinic:polycytidylic acid (poly(I:C)). mRNA expression quantified using qRT-PCR, protein concentrations measured multiplex ELISA. Measurements Main Results: Thirty-nine (n = 20) 19). resulted acid-induced IFN-β both gene (P 0.009) 0.02) levels. IFN-λ also 0.03), whereas IL-33 tended decreased 0.09). On other hand, proinflammatory cytokines IL-6 TNF-α (tumor necrosis factor-α) 0.08) compared group. There no significant changes TSLP (thymic stromal lymphopoietin), IL-4, IL-13, IL-10. Conclusions: improves resistance infection. These results potentially explain efficacy reducing Clinical registered www.clinicaltrials.gov (NCT04100902).

Language: Английский

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Novel adjuvants in allergen-specific immunotherapy: where do we stand?

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

Published: Feb. 23, 2024

Type I hypersensitivity, or so-called type allergy, is caused by Th2-mediated immune responses directed against otherwise harmless environmental antigens. Currently, allergen-specific immunotherapy (AIT) the only disease-modifying treatment with potential to re-establish clinical tolerance towards corresponding allergen(s). However, conventional AIT has certain drawbacks, including long durations, risk of inducing allergic side effects, and fact that allergens themselves have a rather low immunogenicity. To improve AIT, adjuvants can be powerful tool not increase immunogenicity co-applied but also induce desired activation, such as promoting Th1- regulatory responses. This review summarizes knowledge on currently approved for use in human AIT: aluminum hydroxide, calcium phosphate, microcrystalline tyrosine, MPLA, well novel been studied recent years: oil-in-water emulsions, virus-like particles, viral components, carbohydrate-based (QS-21, glucans, mannan) TLR-ligands (flagellin CpG-ODN). The investigated show distinct properties, prolonging allergen release at injection site, IgG production while reducing IgE levels, differentiation activation different cells. In future, better understanding immunological mechanisms underlying effects these settings may help us AIT.

Language: Английский

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Immune signatures predict response to house dust mite subcutaneous immunotherapy in patients with allergic rhinitis

Allergy, Journal Year: 2024, Volume and Issue: 79(5), P. 1230 - 1241

Published: Feb. 25, 2024

Identifying predictive biomarkers for allergen immunotherapy response is crucial enhancing clinical efficacy. This study aims to identify such in patients with allergic rhinitis (AR) undergoing subcutaneous (SCIT) house dust mite allergy.

Language: Английский

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Short-Term Subcutaneous Allergy Immunotherapy and Dupilumab are Well Tolerated in Allergic Rhinitis: A Randomized Trial

Journal of Asthma and Allergy, Journal Year: 2021, Volume and Issue: Volume 14, P. 1045 - 1063

Published: Aug. 1, 2021

Background: Subcutaneous immunotherapy (SCIT) has been proven as an effective therapy against some allergens for seasonal allergic rhinitis (SAR) patients unresponsive to intranasal corticosteroids and/or antihistamines but carries risk of systemic reactions. Dupilumab blocks the shared receptor component interleukin-4 and interleukin-13, key central drivers type 2 inflammation in multiple diseases. Objective: To evaluate efficacy safety SCIT+dupilumab vs SCIT alone. Methods: This phase 2a, multicenter, double-blind, placebo-controlled parallel-group study conducted 103 adults with grass pollen-induced SAR (NCT03558997) randomized 1:1:1:1 SCIT, dupilumab (300 mg every weeks), SCIT+dupilumab, or placebo. was administered using 8-week cluster protocol followed by 8 weeks maintenance injections. Primary endpoint change from pre-treatment baseline area under curve (AUC) total nasal symptom score (TNSS) 0– 1 h following allergen challenge (NAC) timothy extract at Week 17. Results: Although 16 treatment did not significantly improve TNSS AUC (0– h) NAC 17 (least squares mean − 56.76% 52.03%), a higher proportion SCIT+dupilumab-treated (61.5%) achieved dose (46.2%). A lower (7.7%) required epinephrine rescue (19.2%). There were fewer withdrawals group than (n = [7.7%] n [30.8%]; P 0.0216); majority due SCIT-related intolerability, compared no discontinuations group. Conclusion: In patients, may tolerability incrementally reduce post-allergen symptoms Clinical Study Number: NCT03558997. Keywords: dupilumab, rhinitis, subcutaneous immunotherapy, responses

Language: Английский

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Chinese Guideline on Allergen Immunotherapy for Allergic Rhinitis: The 2022 Update

Allergy Asthma and Immunology Research, Journal Year: 2022, Volume and Issue: 14(6), P. 604 - 604

Published: Jan. 1, 2022

In the last few decades, there has been a progressive increase in prevalence of allergic rhinitis (AR) China, where it now affects approximately 250 million people. AR prevention and treatment include allergen avoidance, pharmacotherapy, immunotherapy (AIT), patient education, among which AIT is only curative intervention. targets disease etiology may potentially modify immune system as well induce allergen-specific tolerance patients with AR. 2017, team experts from Chinese Society Allergy (CSA) Allergic Rhinitis Collaborative Research Group (C2AR2G) produced first English version guidelines for Since then, considerable progress basic research clinical practice AIT, especially regarding role follicular regulatory T (TFR) cells pathogenesis use immunoglobulin E (sIgE) nasal secretions diagnosis Additionally, potential biomarkers, including TFR cells, sIgG4, sIgE, have used to monitor incidence progression Moreover, novel understanding during coronavirus 2019 pandemic. Hence, was an urgent need update guideline by CSA C2AR2G. This document aims serve professional reference material on thus improving development across world.

Language: Английский

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Single-cell immunoprofiling after immunotherapy for allergic rhinitis reveals functional suppression of pathogenic TH2 cells and clonal conversion

Journal of Allergy and Clinical Immunology, Journal Year: 2022, Volume and Issue: 150(4), P. 850 - 860.e5

Published: July 19, 2022

Allergic rhinitis is a growing problem worldwide. Currently the only treatment that can modify disease antigen-specific immunotherapy, but its mechanism of action not fully understood.We comprehensively investigated role and changes T cells before after sublingual immunotherapy (SLIT) for Japanese cedar pollinosis.We cultured peripheral blood mononuclear obtained both 1 year initiating SLIT used combination single-cell RNA sequencing repertoire sequencing. To investigate biomarkers, we from patients participating phase 2/3 trial tablets pollinosis outpatients with good poor response.Antigen-stimulated culturing led to clonal expansion TH2 regulatory cells, most these CD4+ retained their CDR3 regions treatment, indicating responses differentiation resulting SLIT. However, reduced number functional increased trans-type cell population expresses musculin (MSC), TGF-β, IL-2. Trajectory analysis suggested induced differentiated into cells. Using real-time PCR, found MSC levels in active group those response treatment.The helped reveal part underlying mechanism: promotes expression on pathogenic suppresses function. may be potential biomarker allergic rhinitis.

Language: Английский

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